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Sample records for dehydro genase g6pd

  1. On the relation between malaria and G-6-PD deficiency

    Science.gov (United States)

    Bottini, E.; Gloria-Bottini, F.; Maggioni, G.

    1978-01-01

    On the basis of the hypothesis that in the regions where favism is present a high correlation exists between endemic malaria and the frequency of G-6-PD deficiency, Huheey and Martin (1975) in a recent paper suggest that the haemolytic event in a malarial environment is a favourable selective factor. Therefore, the fitness of the G-6-PD-deficient individual who shows haemolysis is higher than that of those who do not show haemolysis. Modiano (1976) also suggested that haemolysis may not be a negative component of the selective forces which act on the G-6-PD-deficient variants. In this paper, some facts which make these hypotheses unlikely are considered. Other, more promising, lines for the analysis of the complex relation between malaria and G-6-PD deficiency are suggested. In Sardinia and in the area of the Po Delta, even though favism is present, there is a very low correlation between the frequency of G-6-PD deficiency and past malarial morbidity. Therefore, the situation is similar to that observed in other parts of the world, in which malaria is highly endemic, but where favism is absent. The following facts seem to be in contrast with the possibility that haemolysis could `by itself' be a favourable event: (1) In the hemizygous male, haemolysis due to favism is generally severe and there is a high mortality rate; (2) In the heterozygous female, the erythrocytes with G-6-PD deficiency seem to show a low parasite rate compared to normal cells, and it is just these erythrocytes that are destroyed during the haemolytic crisis; (3) In malarial environments, enzymopenic variants associated with continuous haemolysis have not been selected. A positive selection of such variants would be expected if haemolysis was `by itself' a positive factor. Several observations suggest that the G-6-PD system interacts with various factors, both genetical (thalassaemia, erythrocyte acid phosphatase, adenosine deaminase) and environmental (Vicia Faba, altitude, viral and protozoal

  2. DETECTION OF POINT MUTATIONS IN EXON 2 OF THE G6PD GENE IN CHINESE G6PD VARIANTS

    Institute of Scientific and Technical Information of China (English)

    许卫明; 王菁; 华小云; 杜传书

    1994-01-01

    In the past few years,a total of 6 different mutations of the G6PD gene have been reported in china.One of these,the C6 mutation(A95→G),accounted for about 15.4% of the Chinese G6PD variants.In ordet to develop a strategy for rapid detection of mutation-containing exons of the G6PD gene,we applied the single-strand confor-mation polymorphism(SSCP)technique to the detection of mutations in exon 2 of this gene.We observed four pa-tients with abnormal migration patterns of the exon 2 band among 20 cases of G6PD variants.Direct PCR se-quencing confirmed a Tto C substitution in exon 2 that has previously been reported.This procedure is therefore of particular importance for the rapid detection of mutation-containing exons in the G6PD gene.

  3. A Patient with G6PD Deficiency and Falciparum Malaria

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    Y Fagani

    2007-04-01

    Full Text Available A 20 year old male patient from Afghanistan with a history of G6PD deficiency and clinical manifestations of malaria referred to Bou-Ali Hospital in Tehran, capital of Iran. Giemsa stained thick blood films revealed an infection of Plasmodium falciparum with 33700 parasite/μL of blood. The patient was successfully treated according to malaria treatment guideline.

  4. The Study of G6PD in Erythrocyte and Lens in Senile and Presenile Cataract

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    The G6PD activity of erythrocytes in 113 male patients with senile and presenile cataract and 86 controls, and G6PD activity of lens in 30 patients with senile cataract and 42 controls were reported. The cataractous group had higher frequency of G6PD deficiency and lower average G6PD level in erythrocytes and lenses, but with out statistical significance. The frequency of G6PD deficiency of erythrocytes in presenile cataractous group was higher than that of senile cataractous group but with no statistic...

  5. Glucose-6-phosphate dehydrogenase (G6PD mutations and haemoglobinuria syndrome in the Vietnamese population

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    Day Nick

    2009-07-01

    Full Text Available Abstract Background In Vietnam the blackwater fever syndrome (BWF has been associated with malaria infection, quinine ingestion and G6PD deficiency. The G6PD variants within the Vietnamese Kinh contributing to the disease risk in this population, and more generally to haemoglobinuria, are currently unknown. Method Eighty-two haemoglobinuria patients and 524 healthy controls were screened for G6PD deficiency using either the methylene blue reduction test, the G-6-PDH kit or the micro-methaemoglobin reduction test. The G6PD gene variants were screened using SSCP combined with DNA sequencing in 82 patients with haemoglobinuria, and in 59 healthy controls found to be G6PD deficient. Results This study confirmed that G6PD deficiency is strongly associated with haemoglobinuria (OR = 15, 95% CI [7.7 to 28.9], P G6PD variants were identified in the Vietnamese population, of which two are novel (Vietnam1 [Glu3Lys] and Vietnam2 [Phe66Cys]. G6PD Viangchan [Val291Met], common throughout south-east Asia, accounted for 77% of the variants detected and was significantly associated with haemoglobinuria within G6PD-deficient ethnic Kinh Vietnamese (OR = 5.8 95% CI [114-55.4], P = 0.022. Conclusion The primary frequency of several G6PD mutations, including novel mutations, in the Vietnamese Kinh population are reported and the contribution of G6PD mutations to the development of haemoglobinuria are investigated.

  6. G6PD (AC)n and (CTT)n microsatellites in Mexican Mestizos with common G6PD African variants.

    Science.gov (United States)

    Vaca, Gerardo

    2007-01-01

    Genotyping for the G6PD (AC)n and (CTT)n microsatellites in a sample of 58 Mexican Mestizos with common G6PD African variants was carried out. The second mutation that defines to the variants G6PD A(-202A/376G), G6PD Santamaria(376G/542T) and G6PD A(-376G/968C) very probably occurred on G6PD A(376G) chromosomes with the compound haplotypes, intragenic silent polymorphisms and microsatellites, Pvu-II/Pst-I/Bcl-I/Nla-III/(AC)n/(CTT)n: +/+/-/+/166 bp/195 bp, -/+/-/+/166 bp/201 bp, and -/+/-/+/166 bp/204 bp respectively. The structure of the repeat sequences for the AC-166 bp allele in the 3 variants was (TA)5(AA)1(TA)9(CA)10 whereas the repeat sequences for the CTT-195 bp, CTT-201 bp and CTT-204 bp alleles were (CTT)11(ATT)6, (CTT)7(ATT)12 and (CTT)7(ATT)13 in the first, second and third variants respectively. Genotyping for the G6PD microsatellites can be a useful tool with several applications.

  7. Side Effects of Transfusion of G6PD Deficient Blood in Neonates and Children

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    S.H. Nabavizadeh

    2007-01-01

    Full Text Available Introduction & Objective: Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common metabolic disease of red blood cells. It affects about 35 millions people in the entire world. Its incidence in IRAN is estimated to be 10-14.9%. Transfusion of G6PD deficient blood produces many untoward side effects in recipients. Despite the high incidence of the disease and such risks, blood donors are not screened routinely for this enzyme deficiency. This study performed on effects of G6PD deficient blood in patients admitted in Pediatric & Neonatal ward of Yasouj Emam Sajjad Hospital for detection of proposed side effects. Materials & Methods: Blood samples were obtained from 261 bags of blood during transfusion and the samples were checked for G6PD. Also patients receiving G6PD deficient blood were checked for hemoglobin, serum bilirubin and hemoglobinuria. Factors that tend to hemolysis in G6PD deficient patient were mentioned.Results: 37 (14.7% of samples were G6PD deficient. 81% of donors had at least a risk factor that tend to hemolysis in G6PD deficient state. Side effects of transfusion of G6PD deficient blood included: non significant elevation of hemoglobin (55.9%, hemoglobinuria (35.3% and increase in serum bilirubin (8.8%. Conclusion: It is recommended that in areas where G6PD deficiency is endemic, donors’ blood must be screened before transfusion.

  8. Abrogation of red blood cell G6PD enzyme activity through Heat treatment: development of survey material for the UK NEQAS G6PD scheme.

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    Roper, D R; De la Salle, B; Soni, V; Fletcher, K; Green, J A

    2017-06-01

    Participation in external quality assessment (EQA) is central to the maintenance of high-quality laboratory results in patient diagnosis and clinical trials. Laboratories in the TAF112582 DETECTIVE study (ClinicalTrials.gov identifier: NCT01376167) are enrolled in the United Kingdom National Quality Assessment Scheme (UK NEQAS) for glucose-6-phosphate dehydrogenase (G6PD) quantitative assay, which utilizes ovine (sheep) blood as a readily available source of apparently G6PD-deficient survey material. A substitute for sheep blood was sought because some non-UK sites in the study encountered participation difficulties due to the strict regulations on the import of sheep blood into their countries. G6PD activity in normal human donor blood was abrogated by the action of heat under controlled conditions. Residual G6PD activity in the heated samples was measured by UK NEQAS using the Trinity Biotech 345 kit (Trinity Biotech) and a Jenway 6715 UV/Vis spectrophotometer with external temperature control to monitor enzyme kinetics and linearity over a set time. Heat-treated material was also assayed for G6PD activity and assessed for its acceptability as EQA survey material by selected UK laboratories. Blood heated at 45 °C for 15 h showed a reduction in G6PD activity of 76.3 ± 4.6% (n = 6) and was considered acceptable as EQA material in terms of appearance and behaviour by the majority of UK sites in the trial. We have developed a simple heat-treatment procedure to produce EQA survey material with low/intermediate G6PD activity, similar to that found in females heterozygous for G6PD deficiency. © 2017 The Authors. International Journal of Laboratory Hematology Published by John Wiley & Sons Ltd.

  9. Molecular characterization of a German variant of glucose-6-phosphate dehydrogenase deficiency (G6PD Aachen).

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    Efferth, T; Osieka, R; Beutler, E

    2000-02-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-chromosome-linked hereditary disorder. Clinically, patients with G6PD deficiency often present with drug- or food-induced hemolytic crises or neonatal jaundice. G6PD is involved in the generation of NADPH and reduced glutathione. In contrast to American, Mediterranean, and African ancestries, only few variants are known from Middle and Northern Europe. We describe the molecular characterization of a distinct variant from the northwestern area of Germany, G6PD Aachen. The sequence of the G6PD gene from three afflicted males was found to be hemizygous at cDNA residue 1089 for a C-->G mutation with a predicted amino acid change of Asn363Lys. The 1089 C-->G point mutation is unique, but produces the identical amino acid change found in a Mexican variant of G6PD deficiency, G6PD Loma Linda. This G6PD-deficient variant is caused by a 1089 C-->A mutation. The 363-amino-acid replacement is located outside a known mutation cluster region between amino acid residues 380 and 450, but may disrupt or weaken dimer interactions of G6PD enzyme subunits. Copyright 2000 Academic Press.

  10. Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients

    Institute of Scientific and Technical Information of China (English)

    Manas Kotepui; Kwuntida Uthaisar; Bhukdee PhunPhuech; Nuoil Phiwklam

    2016-01-01

    Background:This study aimed to evaluate the prevalence and alteration of hematological parameters in malaria patients with a glucose-6-phosphate dehydrogenase (G6PD) deficiency,in the western region of Thailand,an endemic region for malaria.Methods:Data about patients with malaria hospitalized between 2013 and 2015 were collected.Clinical and sociodemographic characteristics such as age and gender,diagnosis on admission,and parasitological results were mined from medical records of the laboratory unit of the Phop Phra Hospital in Tak Province,Thailand.Venous blood samples were collected at the time of admission to hospital to determine G6PD deficiency by fluorescence spot test and detect malaria parasites by thick and thin film examination.Other data such as complete blood count and parasite density were also collected and analyzed.Results:Among the 245 malaria cases,28 (11.4 %) were diagnosed as Plasmodium falciparum infections and 217 cases (88.6 %) were diagnosed as P.vivax infections.Seventeen (6.9 %) patients had a G6PD deficiency and 228 (93.1%) patients did not have a G6PD deficiency.Prevalence of male patients with G6PD deficiency was higher than that of female patients (P < 0.05,OR =5.167).Among the patients with a G6PD deficiency,two (11.8 %) were infected with P.falciparum,while the remaining were infected with P.vivax.Malaria patients with a G6PD deficiency have higher monocyte counts (0.6 × 103/μL) than those without a G6PD deficiency (0.33 × 103/μL) (P< 0.05,OR=5.167).Univariate and multivariate analyses also confirmed that malaria patients with a G6PD deficiency have high monocyte counts.The association between G6PD status and monocyte counts was independent of age,gender,nationality,Plasmodium species,and parasite density (P < 0.005).Conclusion:This study showed a prevalence of G6PD deficiency in a malaria-endemic area.This study also supported the assertion that patients with G6PD-deficient red blood cells had no protection

  11. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

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    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  12. Present status of understanding on the G6PD deficiency and natural selection

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    Tripathy V

    2007-01-01

    Full Text Available G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.

  13. Post-operative audit of G6PD-Deficient male children with ...

    African Journals Online (AJOL)

    The fear of possible untoward effects is often expressed by parents of G6PD ... male children between ages 1 to 7years who had adenotonsillectomy over a ... Results: The patients comprised of 22 G6PD deficient male children diagnosed shortly after birth ... Hence, the benefit derived from the surgeries outweighs the risk of ...

  14. Functional and Biochemical Analysis of Glucose-6-Phosphate Dehydrogenase (G6PD Variants: Elucidating the Molecular Basis of G6PD Deficiency

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    Saúl Gómez-Manzo

    2017-05-01

    Full Text Available G6PD deficiency is the most common enzymopathy, leading to alterations in the first step of the pentose phosphate pathway, which interferes with the protection of the erythrocyte against oxidative stress and causes a wide range of clinical symptoms of which hemolysis is one of the most severe. The G6PD deficiency causes several abnormalities that range from asymptomatic individuals to more severe manifestations that can lead to death. Nowadays, only 9.2% of all recognized variants have been related to clinical manifestations. It is important to understand the molecular basis of G6PD deficiency to understand how gene mutations can impact structure, stability, and enzymatic function. In this work, we reviewed and compared the functional and structural data generated through the characterization of 20 G6PD variants using different approaches. These studies showed that severe clinical manifestations of G6PD deficiency were related to mutations that affected the catalytic and structural nicotinamide adenine dinucleotide phosphate (NADPH binding sites, and suggests that the misfolding or instability of the 3D structure of the protein could compromise the half-life of the protein in the erythrocyte and its activity.

  15. The Prevalence of Mediterranean Mutation of Glucose-6-Phosphate Dehydrogenase (G6PD in Zahedan

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    Alireza Nakhaee

    2012-03-01

    Full Text Available Background: glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common genetic defects in the world, so that more than 400 million people in worldwide are affected with it, but its prevalence varies from 1-65% in different populations. Clinical manifestation of this defect is acute hemolytic anemia, neonatal hyperbilirubinemia and chronic nonspherocytic haemolytic anaemia. So far, almost 140 mutations have been identified in the gene of G6PD enzyme. Mediterranean is the most common mutation. The purpose of this study is to determine the prevalence of G6PD Mediterranean mutation in the deficient people in the city of Zahedan.Materials and Methods: In this descriptive cross-sectional study, blood samples of 1440 male individuals, who were referred to Zahedan Reference Laboratory for premarital testing, were examined for G6PD deficiency using fluorescent spot test. Genomic DNA from blood of people with G6PD deficiency was extracted by DNA extraction kit. Mediterranean mutation was identified using PCR-RFLP method.Results: 101 out of 1440 subjects had G6PD deficiency. Therefore prevalence of G6PD deficiency in Zahedan city was estimated about 7%. Mediterranean mutation frequency in patients with defect of G6PD was estimated 84.2% (85 out of 101 patients and 15.8% (16 out of 101 patients did not have mutation Mediterranean. The frequency of G6PD deficiency was expressed as a percentage of total cases and Mediterranean mutation prevalence was expressed as a percentage of total impaired individuals.Conclusion: The result of this study showed that the frequency of G6PD deficiency in Zahedan city is lower than other cities of sistan and baluchestan province. Dominant mutation in present study was Mediterranean type and its frequency was very similar with prevalence of this mutation in other parts of Iran.

  16. Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

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    Zhang, Qiao; Yi, Xiaojia; Yang, Zhe; Han, Qiaoqiao; Di, Xuesong; Chen, Fufei; Wang, Yanling; Yi, Zihan; Kuang, Yingmin; Zhu, Yuechun

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) participates in glucose metabolism and it acts as the rate-limiting enzyme of the pentose phosphate pathway (PPP). Recently, G6PD dysregulation has been found in a variety of human cancers. Through analyzing published data in The Cancer Genome Atlas (TCGA), our pilot study indicated that G6PD mRNA expression was significantly higher in advanced Fuhrman grade in clear cell renal cell carcinoma (ccRCC). These clues promoted us to further evaluate the expression profile of G6PD and its prognostic impact in patients with ccRCC. In this study, G6PD expression levels were analyzed in 149 human ccRCC and normal tissues using immunohistochemistry. The results showed that compared with that in the normal renal samples, G6PD was found highly expressed in 51.0% of ccRCC (p<0.05). High expression of G6PD was significantly correlated to tumor extent, lymph node metastasis, Fuhrman grade, and TNM stage of ccRCC (all p<0.05). Moreover, positive G6PD expression was associated with poorer overall survival in ccRCC (p<0.001). In Cox regression analyses, high expression of G6PD also could be an independent prognostic factor for overall survival in ccRCC (p=0.007). This study suggests that overexpression of G6PD is associated with advanced disease status and therefore may become an important prognosticator for poor outcomes in ccRCC, as well as a potential therapeutic target for developing effective treatment modalities. PMID:28367246

  17. Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition

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    Jonathan W. Nyce

    2017-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is an oncoprotein that is overexpressed in cancer cells to provide the NADPH required for their increased anabolism. NADPH, sourced from G6PD fuels nucleotide biosynthesis, maintains redox potential of thioredoxin and glutathione and drives the mevalonate pathway that powers many of the basic mechanisms by which cancer cells escape host control. G6PD is thus a target for cancer treatment being addressed by many groups around the world. We have discovered that systemic inhibition of G6PD by high dose dehydroepiandrosterone (DHEA causes a severe autoinflammatory response in dogs, which does not occur in mice or rats. Since dogs more closely model the human adrenal androgen system than do common laboratory animals, this finding is relevant to the design of G6PD-inhibiting drugs for humans. The autoinflammatory reaction observed closely resembles mevalonate kinase deficiency (MKD, a rare autosomal recessive disease in humans characterized by recurrent febrile attacks, arthralgia, skin rash, and aphthous ulcers of mucocutaneous tissues. In a manner comparable to animal models of MKD, the reconstitution of protein geranylgeranylation blocked the autoinflammatory reaction caused by systemic G6PD inhibition. This autoinflammatory response to systemic G6PD inhibition represents an unexpected result that must be taken into consideration when targeting this oncoprotein.

  18. Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border.

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    Germana Bancone

    Full Text Available Mutations in the glucose-6-phosphate dehydrogenase (G6PD gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST, G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A genotype. The remaining subjects had Chinese-4 (392G>T, Viangchan (871G>A, Açores (595A>G, Seattle (844G>C and Mediterranean (563C>T variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.

  19. Neonatal Hyperbilirubinemia in infants with G6PD c.563C > TVariant

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    Moiz Bushra

    2012-08-01

    Full Text Available Abstract Background There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. Methods This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing. Results G6PD variants c.563C > T and c.131 C > G were observed in 21 (65% and three (9% of the 32 G6PD deficient infants, respectively. DNA of eight (25% newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p p = 0.008 which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007. No statistically significant

  20. The Effect of Progressive Aerobic Exercise On G6PD Activity Among Active and Sedentary Men

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    Amin Allah Dashtiyan

    2014-10-01

    Full Text Available Background: Erythrocyte glucose–6–phosphate dehydrogenase (G6PD activity is highly associated with free radical production. G6PD deficiency can increase the sensitivity of erythrocytes to oxidative stress resulting in hemolytic anemia. Aim: to study the main effect of progressive aerobic exercise on G6PD activity in active and sedentary men. Material and Methods: the study comprised 10 active men and 10 sedentary men. The protocol, started with running at approximately %75 of their maximal oxygen uptake for 30 min x times a week for y weeks. Venous blood samples (5ml were collected prior to, immediately after, 2 hours and 24 hours after exercise. G6PD activity was evaluated with auto-Analyzer Method. Result: G6PD was not significantly higher in the active men in comparison with the sedentary men at baseline (10.5 ± 1.2 (IU/gHb VS 9.5 ± 1.0 (IU/gHb, P ≤ 0.05. G6PD activity was increased significantly in both groups immediately after exercise but was not considerably different between the groups (11.6 ± 2.7 (IU/gHb VS 9.9 ± 1.1 (IU/gHb, for active and sedentary men, respectively; P ≤ 0.05. G6PD returned to the baseline levels 2 hours after exercise in active men but remained high in sedentary men (10.5 ± 1.4 (IU/gHb VS 10.1 ± 1.1 (IU/gHb, P ≤ 0.05. Also, G6PD levels showed a significant increase 24 hours after exercise in the active men in comparison with the sedentary men (11.8 ± 2.5 (IU/gHb VS 9.5 ± 1.5 (IU/gHb, P ≤ 0.05. Conclusion: In this regard, it can be concluded that, progressive aerobic exercise may be an effective factor affecting the levels of G6PD significantly, and as a home message it is useful for controlling the hemolytic anemia among sedentary population. Keywords: G6PD activity, progressive aerobic exercise, hemolytic anemia

  1. THE ASSOCIATION BETWEEN G6PD DEFICIENCY AND TOTAL SERUM BILIRUBIN LEVEL IN ICTERIC NEONATES

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    S. Behjati-Ardakani

    2007-07-01

    Full Text Available "nGlucose-6-phosphate dehydrogenase (G6PD deficiency is the most important disease of the hexose monophosphate pathway. Deficiency of this enzym can lead to hemolysis of red blood cells. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice. We studied 456 clinically icteric neonates Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct coomb's test, hemoglobin, blood smear, reticulocyte count and G6PD level. We divided these neonates to 3 groups based on total serum bilirubin level (TSB: TSB< 20 mg%, TSB=20-25 mg%, and TSB>25 mg%. In only 35 (7.6% of cases G6PD deficiency was diagnosed. All of these babies were male. From 456 icteric neonates, 213 cases belong to group 1 (TSB<20 mg%, 158 cases belong to group 2 (TSB=20-25 mg% and 85 cases belong to group 3 (TSB>25 mg%. 16 neonates from 213 neonates of group 1, 6 neonates from 158 neonates of group 2 and 13 neonates from 85 neonates of group 3 had G6PD deficiency. There was statistically significant difference of prevalence of G6PD deficiency between group 2 and 3 ( 15.3% vs 3.8%( P = 0.001. Between groups 1 vs 2 and 1 vs 3 no statistically significant difference was found. Early detection of this enzymopathy regardless of sex and close surveillance of the affected newborns may be important in reducing the risk of severe hyperbilirubinemia. This emphasizes the necessity of neonatal screening on cord blood samples for G6PD deficiency.

  2. A novel point mutation in a class IV glucose-6-phosphate dehydrogenase variant (G6PD São Paulo and polymorphic G6PD variants in São Paulo State, Brazil

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    Raimundo Antonio G. Oliveira

    2009-01-01

    Full Text Available In this study, we used red cell glucose-6-phosphate dehydrogenase (G6PD activity to screen for G6PD-deficient individuals in 373 unrelated asymptomatic adult men who were working with insecticides (organophosphorus and carbamate in dengue prevention programs in 27 cities in São Paulo State, Brazil. Twenty-one unrelated male children suspected of having erythroenzymopathy who were attended at hospitals in São Paulo city were also studied. Fifteen of the 373 adults and 12 of the 21 children were G6PD deficient. G6PD gene mutations were investigated in these G6PD-deficient individuals by using PCR-RFLP, PCR-SSCP analysis and DNA sequencing. Twelve G6PD A-202A/376G and two G6PD Seattle844C, as well as a new variant identified as G6PD São Paulo, were detected among adults, and 11 G6PD A-202A/376G and one G6PD Seattle844C were found among children. The novel mutation c.660C > G caused the replacement of isoleucine by methionine (I220M in a region near the dimer interface of the molecule. The conservative nature of this mutation (substitution of a nonpolar aliphatic amino acid for another one could explain why there was no corresponding change in the loss of G6PD activity (64.5% of normal activity in both cases.

  3. G6PD deficiency: global distribution, genetic variants and primaquine therapy.

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    Howes, Rosalind E; Battle, Katherine E; Satyagraha, Ari W; Baird, J Kevin; Hay, Simon I

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a potentially pathogenic inherited enzyme abnormality and, similar to other human red blood cell polymorphisms, is particularly prevalent in historically malaria endemic countries. The spatial extent of Plasmodium vivax malaria overlaps widely with that of G6PD deficiency; unfortunately the only drug licensed for the radical cure and relapse prevention of P. vivax, primaquine, can trigger severe haemolytic anaemia in G6PD deficient individuals. This chapter reviews the past and current data on this unique pharmacogenetic association, which is becoming increasingly important as several nations now consider strategies to eliminate malaria transmission rather than control its clinical burden. G6PD deficiency is a highly variable disorder, in terms of spatial heterogeneity in prevalence and molecular variants, as well as its interactions with P. vivax and primaquine. Consideration of factors including aspects of basic physiology, diagnosis, and clinical triggers of primaquine-induced haemolysis is required to assess the risks and benefits of applying primaquine in various geographic and demographic settings. Given that haemolytically toxic antirelapse drugs will likely be the only therapeutic options for the coming decade, it is clear that we need to understand in depth G6PD deficiency and primaquine-induced haemolysis to determine safe and effective therapeutic strategies to overcome this hurdle and achieve malaria elimination.

  4. Glucose-6-phosphate dehydrogenase (G6PD) deficiency among tribal populations of India - Country scenario

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    Mukherjee, Malay B.; Colah, Roshan B; Martin, Snehal; Ghosh, Kanjaksha

    2015-01-01

    It is believed that the tribal people, who constitute 8.6 per cent of the total population (2011 census of India), are the original inhabitants of India. Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity. Deficiency of this enzyme is highly polymorphic in those areas where malaria is/has been endemic. G6PD deficiency was reported from Indi...

  5. Chronic nonspherocytic hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency: report of two families with novel mutations causing G6PD Bangkok and G6PD Bangkok Noi.

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    Tanphaichitr, Voravarn S; Hirono, Akira; Pung-amritt, Parichat; Treesucon, Ajjima; Wanachiwanawin, Wanchai

    2011-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymopathies worldwide. Mostly G6PD deficient cases are asymptomatic though they may have the risk of neonatal jaundice (NNJ) and acute intravascular hemolysis during oxidative stress. Chronic nonspherocytic hemolytic anemia (CNSHA) due to G6PD deficiency is rare. In Thailand, one case was reported 40 years ago and by biochemical study this G6PD was reported to be a new variant G6PD Bangkok. We, herein, report two families with CNSHA due to G6PD deficiency. In the first family, we have been following up the clinical course of the patient with G6PD Bangkok. In addition to chronic hemolysis, he had three acute hemolytic episodes requiring blood transfusions during childhood period. Multiple gallstones were detected at the age of 27. His two daughters who inherited G6PD Bangkok from him and G6PD Vanua Lava from his wife are asymptomatic. Both of them had NNJ and persistent evidences of compensated hemolysis. Molecular analysis revealed a novel missense mutation 825 G→C predicting 275 Lys→Asn causing G6PD Bangkok. In the second family, two male siblings are affected. They had NNJ and several hemolytic episodes which required blood transfusions. On follow-up they have been diagnosed with chronic hemolysis as evidenced by reticulocytosis and indirect hyperbilirubinemia. Molecular analysis revealed combined missense mutations in exons 12 and 13. The first mutation was 1376 G→T predicting 459 Arg→Leu (known as G6PD Canton) and the second one was 1502 T→G predicting 501 Phe→Cys. We designated the resulting novel G6PD variant, G6PD Bangkok Noi.

  6. Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD-deficient human fibroblasts

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    Wu Yi-Hsuan

    2009-02-01

    Full Text Available Abstract Fibroblasts derived from glucose-6-phosphate dehydrogenase (G6PD-deficient patients display retarded growth and accelerated cellular senescence that is attributable to increased accumulation of oxidative DNA damage and increased sensitivity to oxidant-induced senescence, but not to accelerated telomere attrition. Here, we show that ectopic expression of hTERT stimulates telomerase activity and prevents accelerated senescence in G6PD-deficient cells. Stable clones derived from hTERT-expressing normal and G6PD-deficient fibroblasts have normal karyotypes, and display no sign of senescence beyond 145 and 105 passages, respectively. Activation of telomerase, however, does not prevent telomere attrition in earlier-passage cells, but does stabilize telomere lengths at later passages. In addition, we provide evidence that ectopic expression of hTERT attenuates the increased sensitivity of G6PD-deficient fibroblasts to oxidant-induced senescence. These results suggest that ectopic expression of hTERT, in addition to acting in telomere length maintenance by activating telomerase, also functions in regulating senescence induction.

  7. O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth.

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    Rao, Xiongjian; Duan, Xiaotao; Mao, Weimin; Li, Xuexia; Li, Zhonghua; Li, Qian; Zheng, Zhiguo; Xu, Haimiao; Chen, Min; Wang, Peng G; Wang, Yingjie; Shen, Binghui; Yi, Wen

    2015-09-24

    The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. Importantly, G6PD glycosylation is increased in human lung cancers. Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours.

  8. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

    OpenAIRE

    Mueller, Ivo; MalariaGEN Consortium

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study ...

  9. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study

    Science.gov (United States)

    Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N.; Khan, Wasif Ali

    2016-01-01

    Background The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Methods Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0–2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0–2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Results Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2–27.3) hours for P. falciparum, 20.0 (IQR: 9.5–22.7) hours for P. vivax and 16.6 (IQR: 10.0–46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10–60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. Conclusion The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal

  10. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study.

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    Benedikt Ley

    Full Text Available The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2 plus single dose primaquine (0.75mg/kg on day2 for P. falciparum infections, or with chloroquine (days 0-2 plus 14 days primaquine (3.5mg/kg total over 14 days for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374.Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections. Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3 hours for P. falciparum, 20.0 (IQR: 9.5-22.7 hours for P. vivax and 16.6 (IQR: 10.0-46.0 hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174 had severe G6PD deficiency (<10% activity, five participants (5/174 had mild G6PD deficiency (10-60% activity. The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0% and -7.4% (95%CI: -4.5 to -10.4% respectively.The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather

  11. G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.

    Science.gov (United States)

    Dombrowski, Jamille G; Souza, Rodrigo M; Curry, Jonathan; Hinton, Laura; Silva, Natercia R M; Grignard, Lynn; Gonçalves, Ligia A; Gomes, Ana Rita; Epiphanio, Sabrina; Drakeley, Chris; Huggett, Jim; Clark, Taane G; Campino, Susana; Marinho, Claudio R F

    2017-06-15

    Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection. Five-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay. Twenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups. The data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur

  12. G6pd Deficiency Does Not Affect the Cytosolic Glutathione or Thioredoxin Antioxidant Defense in Mouse Cochlea.

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    White, Karessa; Kim, Mi-Jung; Ding, Dalian; Han, Chul; Park, Hyo-Jin; Meneses, Zaimary; Tanokura, Masaru; Linser, Paul; Salvi, Richard; Someya, Shinichi

    2017-06-07

    Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. We investigated the roles of G6PD in the cytosolic antioxidant defense in the cochlea of G6pd hypomorphic mice that were backcrossed onto normal-hearing CBA/CaJ mice. Young G6pd-deficient mice displayed a significant decrease in cytosolic G6PD protein levels and activities in the inner ears. However, G6pd deficiency did not affect the cytosolic NADPH redox state, or glutathione or thioredoxin antioxidant defense in the inner ears. No histological abnormalities or oxidative damage was observed in the cochlea of G6pd hemizygous males or homozygous females. Furthermore, G6pd deficiency did not affect auditory brainstem response hearing thresholds, wave I amplitudes or wave I latencies in young males or females. In contrast, G6pd deficiency resulted in increased activities and protein levels of cytosolic isocitrate dehydrogenase 1, an enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate and NADP(+) to NADPH, in the inner ear. In a mouse inner ear cell line, knockdown of Idh1, but not G6pd, decreased cell growth rates, cytosolic NADPH levels, and thioredoxin reductase activities. Therefore, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in mouse cochlea. Under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea.SIGNIFICANCE STATEMENT Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH and

  13. Perioperative challenges in a patient of severe G6PD deficiency undergoing open heart surgery

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    Vivek Chowdhry

    2012-01-01

    Full Text Available We describe a successful perioperative management of a case of 38-year-old male, presented with chronic jaundice with severe mitral stenosis and moderate tricuspid regurgitation; upon evaluation, he was found to have severe glucose-6-phosphate dehydrogenase (G6PD deficiency. Usually, patients deficient in G6PD exhibit increased hemolysis andtherefore increased need for blood transfusion after cardiac surgery as well as impaired oxygenation in the postoperative period leading to prolonged ventilation. On reperfusion after a period of ischemia, the antioxidant system recruits all of its components in an attempt to neutralize the overwhelming oxidative stress of free radicals, as the free radical scavenging system is deficient in these patients, the chances of free-radical-induced injury is more. Our patient underwent mitral valve replacement and tricuspid annuloplasty under cardiopulmonary bypass with necessary precautions to reduce the formation of free radicals. Treatment was targeted toward theprevention of free radical injuryin the G6PD-deficient patient. He had an uneventful intraoperative and postoperative course.

  14. The Stability of G6PD Is Affected by Mutations with Different Clinical Phenotypes

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    Saúl Gómez-Manzo

    2014-11-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzyme deficiency worldwide, causing a wide spectrum of conditions with severity classified from the mildest (Class IV to the most severe (Class I. To correlate mutation sites in the G6PD with the resulting phenotypes, we studied four naturally occurring G6PD variants: Yucatan, Nashville, Valladolid and Mexico City. For this purpose, we developed a successful over-expression method that constitutes an easier and more precise method for obtaining and characterizing these enzymes. The kcat (catalytic constant of all the studied variants was lower than in the wild-type. The structural rigidity might be the cause and the most evident consequence of the mutations is their impact on protein stability and folding, as can be observed from the protein yield, the T50 (temperature where 50% of its original activity is retained values, and differences on hydrophobic regions. The mutations corresponding to more severe phenotypes are related to the structural NADP+ region. This was clearly observed for the Classes III and II variants, which became more thermostable with increasing NADP+, whereas the Class I variants remained thermolabile. The mutations produce repulsive electric charges that, in the case of the Yucatan variant, promote increased disorder of the C-terminus and consequently affect the binding of NADP+, leading to enzyme instability.

  15. Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia.

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    Ari W Satyagraha

    2016-02-01

    Full Text Available Patients infected by Plasmodium vivax or Plasmodium ovale suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated.This device and the standard qualitative fluorescent spot test (FST were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity ≥ 5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively.The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance among females due to mosaic G6PD phenotype is an

  16. Glucose-6-phosphate dehydrogenase (G6PD-deficient epithelial cells are less tolerant to infection by Staphylococcus aureus.

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    Yi-Ting Hsieh

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.

  17. Modeling Plasmodium vivax: relapses, treatment, seasonality, and G6PD deficiency.

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    Chamchod, Farida; Beier, John C

    2013-01-07

    Plasmodium vivax (P. vivax) is one of the most important human malaria species that is geographically widely endemic and causes social and economic burden globally. However, its consequences have long been neglected and underestimated as it has been mistakenly considered a benign and inconsequential malaria species as compared to Plasmodium falciparum. One of the important differences between P. falciparum and P. vivax is the formation of P. vivax latent-stage parasites (hypnozoites) that can cause relapses after a course of treatment. In this work, mathematical modeling is employed to investigate how patterns of incubation periods and relapses of P. vivax, variation in treatment, and seasonal abundance of mosquitoes influence the number of humans infected with P. vivax and the mean age at infection of humans in tropical and temperate regions. The model predicts that: (i) the number of humans infected with P. vivax may increase when an incubation period of parasites in humans and a latent period of hypnozoites decrease; (ii) without primaquine, the only licensed drug to prevent relapses, P. vivax may be highly prevalent; (iii) the mean age at infection of humans may increase when a latent period of hypnozoites increases; (iv) the number of infectious humans may peak at a few months before the middle of each dry season and the number of hypnozoite carriers may peak at nearly the middle of each dry season. In addition, glucose-6-phosphate-dehydrogenase (G6PD) deficiency, which is the most common enzyme defect in humans that may provide some protection against P. vivax infection and severity, is taken into account to study its impact on the number of humans infected with P. vivax. Modeling results indicate that the increased number of infected humans may result from a combination of a larger proportion of humans with G6PD deficiency in the population, a lesser protection of G6PD deficiency to P. vivax infection, and a shorter latent period of hypnozoites.

  18. Interesting case of G6PD deficiency anemia with severe hemolysis

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    Anupam Chhabra

    2013-01-01

    Full Text Available Severe hemolysis was observed in a critically ill patient with G6Pd deficiency where the causative trigger could not be identified. We describe one young patient with severe hemolysis treated with two cycles of plasmapheresis which proved to be an effective tool in the treatment. The patient presented with diffuse pain abdomen, vomiting, yellowish discoloration of sclera and skin and acute breathlessness. Hemoglobin 5.4 mg/dl and total (T serum bilirubin 17.08 mg/dl: Direct (D 4.10 mg/dl and Indirect (I 12.98 mg/dl. Subsequently patient started passing black color urine. As the patient developed severe hemolysis and the trigger agent of hemolysis was unknown, two cycles of plasmapheresis were performed with the aim to remove unknown causative agent. Consequently no trace of hemolysis was found and patient stabilized. Plasmapheresis can be used to treat G6PD deficient patients with severe hemolysis due to unidentified trigger agent.

  19. Precautionary Measures for Successful Open Heart Surgery in G6PD Deficient Patient- A Case Report

    Science.gov (United States)

    2016-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is among the most common enzymatic disorders of red blood cells. Cardiac surgeries on this group of individuals are associated with an additional risk in terms of impaired oxygenation, prolonged ventilation and increased risk of haemolysis. These patients have a very low threshold for haemolysis due to oxidative stress. Many commonly used drugs also predispose the individual for haemolysis when they are subjected to surgery. Here we present a known case of G6PD deficient patient with symptoms of breathlessness for the last nine years who was taken for surgery with pre-planned precautionary measures to avoid unnecessary haemolysis. The echocardiography report revealed severe mixed mitral lesion and moderate tricuspid regurgitation. On general examination she had mild pallor and icterus. We planned for a thorough investigation to prepare her for mitral valve replacement and tricuspid annuloplasty. These groups of patients are at high risk of haemolysis during perioperative period and need prolonged mechanical ventilation and hospital stay due to impaired oxygen carrying capacity and oxidative stress due to deficient free radical scavenging system. The patient underwent mechanical mitral valve replacement and tricuspid annuloplasty under cardiopulmonary bypass with precautionary measures to prevent the risk of haemolysis and associated complications. She had an uneventful recovery. PMID:28208930

  20. Phenotypic and quantitative relationship of red cell acid phosphatase with haemoglobin, haptoglobin, and G6PD phenotypes.

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    Saha, N; Patgunarajah, N

    1981-08-01

    The phenotypic and quantitative relationship of red cell acid phosphatase with haemoglobin, haptoglobin, and G6PD phenotypes was investigated in three populations in the Sudan and one population in Nilgiris, India. No significant consistent association of red cell acid phosphatase phenotypes was observed with these polymorphisms. However, there was a lack of acid phosphatase AB in G6PD deficient subjects from Nilgiris. The relative quantitative expression of red cell acid phosphatase genes PA, PB, and PC was 1.0, 1.2, and 1.3, respectively. The red cell acid phosphatase activity was higher (15%) in the presence of raised haemoglobin A2 and in sickle cell anaemia (21%). Those with Hp2 had 18% higher level of acid phosphatase than those with Hp1. G6PD deficient subjects had a lower level of acid phosphatase activity (20%) than those with normal G6PD activity.

  1. A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

    Science.gov (United States)

    Boonyuen, Usa; Chamchoy, Kamonwan; Swangsri, Thitiluck; Junkree, Thanyaphorn; Day, Nicholas P J; White, Nicholas J; Imwong, Mallika

    2017-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown. In this study, we report the construction, expression, purification, and biochemical characterization in terms of kinetic properties and stability of five clinical G6PD variants-G6PD Bangkok, G6PD Bangkok noi, G6PD Songklanagarind, G6PD Canton+Bangkok noi, and G6PD Union+Viangchan. G6PD Bangkok and G6PD Canton+Bangkok noi showed a complete loss of catalytic activity and moderate reduction in thermal stability when compared with the native G6PD. G6PD Bangkok noi and G6PD Union+Viangchan showed a significant reduction in catalytic efficiency, whereas G6PD Songklanagarind showed a catalytic activity comparable to the wild-type enzyme. The Union+Viangchan mutation showed a remarkable effect on the global stability of the enzyme. In addition, our results indicate that the location of mutations in G6PD variants affects their catalytic activity, stability, and structure. Hence, our results provide a molecular explanation for clinical manifestations observed in individuals with G6PD deficiency. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso

    Institute of Scientific and Technical Information of China (English)

    Abdoul Karim Ouattara; Cyrille Bisseye; Birama Diarra; Tegwind Rebeca Compaore; Florencia Djigma; Virginio Pietra; Remy Moret; Jacques Simpore

    2014-01-01

    Objective: To investigate 4 combinations of mutations responsible for glucose-6-phosphate dehydrogenase (G6PD) deficiency in a rural community of Burkina Faso, a malaria endemic country. Methods: Two hundred individuals in a rural community were genotyped for the mutations A376G, G202A, A542T, G680T and T968C using TaqMan single nucleotide polymorphism assays and polymerase chain reaction followed by restriction fragment length polymorphism. Results: The prevalence of the G6PD deficiency was 9.5% in the study population. It was significantly higher in men compared to women (14.3%vs 6.0%, P=0.049). The 202A/376G G6PD A-was the only deficient variant detected. Plasmodium falciparum asymptomatic parasitaemia was significantly higher among the G6PD-non-deficient persons compared to the G6PD-deficient (P Conclusions:This study showed that the G6PD A-variant associated with protection against asymptomatic malaria in Burkina Faso is probably the most common deficient variant.

  3. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

    Science.gov (United States)

    Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy ME; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris CA; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations. DOI: http://dx.doi.org/10.7554/eLife.15085.001 PMID:28067620

  4. Field trial evaluation of the performances of point-of-care tests for screening G6PD deficiency in Cambodia.

    Directory of Open Access Journals (Sweden)

    Arantxa Roca-Feltrer

    Full Text Available User-friendly, accurate, point-of-care rapid tests to detect glucose-6-phosphate dehydrogenase deficiency (G6PDd are urgently needed at peripheral level to safely recommend primaquine for malaria elimination.The CareStart G6PD RDT (AccessBio, New Jersey, USA, a novel rapid diagnostic test and the most commonly used test, the fluorescent spot test (FST were assessed against the quantitatively measured G6PD enzyme activity for detecting G6PDd. Subjects were healthy males and non-pregnant females aged 18 years or older residing in six villages in Pailin Province, western Cambodia.Of the 938 subjects recruited, 74 (7.9% were severe and moderately severe G6PD deficient (enzyme activity <30%, mostly in male population; population median G6PD activity was 12.0 UI/g Hb. The performances of the CareStart G6PD RDT and the FST, according to different cut-off values used to define G6PDd were very similar. For the detection of severe and moderately severe G6PDd (enzyme activity < 30%, < 3.6 UI/g Hb in males and females, sensitivity and negative (normal status predictive value were 100% for both point-of-care tools. When the G6PDd cut-off value increased (from < 40% to < 60%, the sensitivity for both PoCs decreased: 93.3% to 71.7% (CareStart G6PD RDT, p = 10(-6 and 95.5% to 73.2% (FST, p = 10(-6 while the specificity for both PoCs remained similar: 97.4% to 98.3% (CareStart G6PD RDT, p = 0.23 and 98.7% to 99.6% (FST, p = 0.06. The cut-off values for classifying individuals as normal were 4.0 UI/g Hb and 4.3 UI/g Hb for the CareStart G6PD RDT and the FST, respectively.The CareStart G6PD RDT reliably detected moderate and severe G6PD deficient individuals (enzyme activity <30%, suggesting that this novel point-of-care is a promising tool for tailoring appropriate primaquine treatment for malaria elimination by excluding individuals with severe G6PDd for primaquine treatment.

  5. Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka

    Science.gov (United States)

    Kapilananda, G. M. G.; Samarakoon, Dilhani; Maddevithana, Sashika; Wijesundera, Sulochana; Goonaratne, Lallindra V.; Karunaweera, Nadira D.

    2017-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filter-paper blood spots collected between November 2013 and June 2014 were analysed for phenotypic G6PD deficiency using the modified WST-8/1-methoxy PMS method. Each assay was conducted with a set of controls and the colour development assessed visually as well as with a microplate reader at OD450-630nm. Overall, 142/1018 (13.95%) and 83/1041 (7.97%) were G6PD deficient in Anuradhapura and Kurunegala districts respectively. The G6PD prevalence was significantly greater in Anuradhapura when compared to Kurunegala (P0.05). Severe deficiency (<10% normal) was seen among 28/1018 (2.75%) in Anuradhapura (7 males; 21 females) and 17/1041 (1.63%) in Kurunegala (7 males; 10 females). Enzyme activity between 10–30% was observed among 114/1018 (11.20%; 28 males; 86 females) in Anuradhapura while it was 66/1041 (6.34%; 18 males; 48 females) in Kurunegala. Screening and educational programmes for G6PD deficiency are warranted in these high risk areas irrespective of gender for the prevention of disease states related to this condition. PMID:28152025

  6. G6PD haplotypes spanning Xq28 from F8C to red/green color vision

    Energy Technology Data Exchange (ETDEWEB)

    Filosa, S.; Lania, G.; Martini, G. (Instituto Internazionale di Genetica e Biofisica, Naples (Italy)); Brancati, C.; Tagarelli, A. (Instituto per lo Studio delle Malattie Ereditarie e Carenziali, Cosenza (Italy)); Calabro, V. (Instituto per lo Studio delle Malattie Ereditarie e Carenziali, Cosenza (Italy) Hammersmith Hospital, London (United Kingdom)); Vulliamy, T.J.; Luzzatto, L. (Hammersmith Hospital, London (United Kingdom))

    1993-07-01

    The most telomeric region of the human X chromosome within band Xq28 consists of a gene-rich region of about 3 Mb which contains the genes for coagulation factor VIIIc, glucose-6-phosphate dehydrogenase (G6PD), and red/green color vision. The authors have studied five polymorphic sites from this region, in a sample of normal people from the Cosenza province of Southern Italy. These sites, which span a distance of some 350 kb, are in strong linkage disequilibrium. Of the 32 possible haplotypes only 10 were found, and 4 of these account for 80% of all X chromosomes analyzed. In addition, they found that all G6PD-deficient people with the G6PD Mediterranean mutation belong to only two haplotypes. One of these (Med 1) is found only within a small subregion of the area investigated, west of the Appennine mountain range. Most remarkably, all Med 1 G6PD-deficient individuals also had red/green color blindness. The more frequent haplotype (Med 2) is the same in Calabria and in Sardinia, where it accounts for about 90% of the G6PD Mediterranean mutations, despite the fact that gene flow between the populations of Sardinia and Southern Italy must have been limited. These data do not enable determination of whether the two types of G6PD Mediterranean have arisen through two separate identical mutational events or through a single mutational event followed by recombination. However, the data indicate relatively little recombination over an extended region of the X chromosome and they suggest that the G6PD Mediterranean mutation is recent by comparison to the other polymorphisms investigated. 44 refs., 4 figs., 5 tabs.

  7. High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A- deficiency.

    Directory of Open Access Journals (Sweden)

    Caterina I Fanello

    Full Text Available BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. METHODS: The safety of chlorproguanil-dapsone+artesunate (CD+A and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. FINDINGS: In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33 and 1.05% per day (95% CI 0.95 to 1.15 respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25 to 1.45. Patients with G6PD deficiency recipients of CD+A had significantly lower haematocrit than the other groups until day 7 (p = 0.04. In total, 10 patients had severe post-treatment haemolysis requiring blood transfusion. Patients with G6PD deficiency showed a higher risk of severe anaemia following treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3 or AQ+SP (RR = 5.6; 95% CI 1.0 to 32.7. CONCLUSIONS: CD+A showed a poor safety profile in individuals with G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary.

  8. Aspectos laboratoriais do diagnóstico da deficiência de glicose-6-fosfato desidrogenase (G6PD)

    OpenAIRE

    Simone Martins Castro

    2006-01-01

    A G6PD é expressa em todos os tecidos, onde catalisa a primeira etapa da via das pentoses-fosfato. O NADPH produzido pela ação da G6PD serve como doador de elétrons na biossíntese redutora. Pelo fato de os glóbulos vermelhos não terem mitocôndria, a via das pentoses-fosfato é a única fonte de NADPH e essencial para sua proteção contra o stress oxidativo. A deficiência da G6PD é classificada como anemia hemolítica hereditária ligada ao cromossomo X, associada a manifestações clínicas heterogên...

  9. G6PD deficiency in Latin America: systematic review on prevalence and variants

    Science.gov (United States)

    Monteiro, Wuelton M; Val, Fernando FA; Siqueira, André M; Franca, Gabriel P; Sampaio, Vanderson S; Melo, Gisely C; Almeida, Anne CG; Brito, Marcelo AM; Peixoto, Henry M; Fuller, Douglas; Bassat, Quique; Romero, Gustavo AS; Maria Regina F, Oliveira; Marcus Vinícius G, Lacerda

    2014-01-01

    Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available. PMID:25141282

  10. G6PD deficiency in Latin America: systematic review on prevalence and variants

    Directory of Open Access Journals (Sweden)

    Wuelton M Monteiro

    2014-08-01

    Full Text Available Plasmodium vivax radical cure requires the use of primaquine (PQ, a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10% of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

  11. A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong Hill Tracts, Bangladesh

    Science.gov (United States)

    Ley, Benedikt; Alam, Mohammad Shafiul; O’Donnell, James J.; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Jahan, Nusrat; Khan, Wasif A.; Thriemer, Kamala; Chatfield, Mark D.; Price, Ric N.; Richards, Jack S.

    2017-01-01

    Background Glucose-6-phosphate-dehydrogenase-deficiency (G6PDd) is a major risk factor for primaquine-induced haemolysis. There is a need for improved point-of-care and laboratory-based G6PD diagnostics to unsure safe use of primaquine. Methods G6PD activities of participants in a cross-sectional survey in Bangladesh were assessed using two novel quantitative assays, the modified WST-8 test and the CareStart™ G6PD Biosensor (Access Bio), The results were compared with a gold standard UV spectrophotometry assay (Randox). The handheld CareStart™ Hb instrument (Access Bio) is designed to be a companion instrument to the CareStart™ G6PD biosensor, and its performance was compared to the well-validated HemoCue™ method. All quantitative G6PD results were normalized with the HemoCue™ result. Results A total of 1002 individuals were enrolled. The adjusted male median (AMM) derived by spectrophotometry was 7.03 U/g Hb (interquartile range (IQR): 5.38–8.69), by WST-8 was 7.03 U/g Hb (IQR: 5.22–8.16) and by Biosensor was 8.61 U/g Hb (IQR: 6.71–10.08). The AMM between spectrophotometry and WST-8 did not differ (p = 1.0) but differed significantly between spectrophotometry and Biosensor (p0.05). Sensitivity and specificity for detecting G6PD activity <30% was 0.55 (95% confidence interval (95%CI): 0.44–0.66) and 0.98 (95%CI: 0.97–0.99) respectively for the WST-8 and 0.19 (95%CI: 0.12–0.29) and 0.99 (95%CI: 0.98–0.99) respectively for the Biosensor. Hb concentrations measured by HemoCue™ and CareStart™ Hb were strongly correlated (rs = 0.8, p<0.001, mean difference = 0.09 g Hb/dL, 95% LoA: -2.15 to 2.34). Conclusion WST-8 and the CareStart™ G6PD Biosensor represent advances in G6PD diagnostics in resource poor settings, but will require further development before clinical deployment. The CareStart™ Hb instrument produced a precise measure of haemoglobin concentration. PMID:28121993

  12. Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD-null): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress.

    NARCIS (Netherlands)

    P.P. Pandolfi; F. Sonati; R. Rivi; P. Mason; F.G. Grosveld (Frank); L. Luzzatto

    1995-01-01

    textabstractGlucose 6-phosphate dehydrogenase (G6PD) is a housekeeping enzyme encoded in mammals by an X-linked gene. It has important functions in intermediary metabolism because it catalyzes the first step in the pentose phosphate pathway and provides reductive potential in the form of NADPH. In h

  13. Nine Different Glucose-6-phosphate Dehydrogenase (G6PD Variants in a Malaysian Population with Malay, Chinese, Indian and Orang Asli (Aboriginal Malaysian Backgrounds

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    Isa,Zaleha Mohamed

    2008-10-01

    Full Text Available The Malaysian people consist of several ethnic groups including the Malay, the Chinese, the Indian and the Orang Asli (aboriginal Malaysians. We collected blood samples from outpatients of 2 hospitals in the State of Selangor and identified 27 glucose-6-phosphate dehydrogenase (G6PD-deficient subjects among these ethnic groups. In the Malay, G6PD Viangchan (871G>A, 1311C>T, IVS11 nt93T>C and G6PD Mahidol (487G>A types, which are common in Cambodia and Myanmar, respectively, were detected. The Malay also had both subtypes of G6PD Mediterranean:the Mediterranean subtype (563C>T, 1311C>T, IVS11 nt93T>C and the Indo-Pakistan subtype (563C>T, 1311C, IVS11 nt93T. In Malaysians of Chinese background, G6PD Kaiping (1388G>A, G6PD Canton (1376G>T and G6PD Gaohe (95A>G, which are common in China, were detected. Indian Malaysians possessed G6PD Mediterranean (Indo-Pakistan subtype and G6PD Namoru (208T>C, a few cases of which had been reported in Vanuatu and many in India. Our findings indicate that G6PD Namoru occurs in India and flows to Malaysia up to Vanuatu. We also discovered 5 G6PD-deficient cases with 2 nucleotide substitutions of 1311C>T and IVS11 nt93T>C, but without amino-acid substitution in the G6PD molecule. These results indicate that the Malaysian people have incorporated many ancestors in terms of G6PD variants.

  14. Influence of dehydroepiandrosterone on G-6-PD activity and /sup 3/H-thymidine uptake of human lymphocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ennas, M.G.; Laconi, S.; Dessi, S.; Milia, G.; Murru, M.R.; Manconi, P.E.

    1987-01-01

    Dehydroepiandrosterone (DHEA) was found to inhibit experimental cancer development in mouse and rat lung, colon and mammary gland. Since DHEA is a potent inhibitor of mammalian G-6-PD, the hypothesis that the compound could inhibit cell proliferation through an inhibition of the pentose phosphate pathway has been formulated. We studied the effects of DHEA on the proliferation in vitro of human lymphocytes induced by several mitogens (PHA, ConA and PWM), measuring /sup 3/H-thymidine uptake. DHEA inhibited /sup 3/H-thymidine uptake of mitogen-stimulated cells from both G-6-PD+ and G-6-PD- (mediterranean type deficiency) individuals in a dose-dependent and reversible fashion. The inhibitory effect was found even if DHEA was added to cells in the last hours of culture, simultaneously with the addition of /sup 3/H-thymidine. These data suggest that the inhibition of thymidine uptake induced by DHEA on human lymphocytes probably does not depend on the inhibition of G-6-PD.

  15. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency.

    Science.gov (United States)

    Sirdah, Mahmoud M; Shubair, Mohammad E; Al-Kahlout, Mustafa S; Al-Tayeb, Jamal M; Prchal, Josef T; Reading, N Scott

    2017-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

  16. Survey of the Prevalence of Glucose-6-Phosphate Dehydrogenase (G6PD Deficiency in Admitted Men for Premarriage Tests in Zahedan-Iran Reference Laboratory

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    Nakhaee Ali Reza

    2009-09-01

    Full Text Available Background: GLucose-6-phosphate dehydrogenase (G6PD deficiency is the most common known enzymopathy in human. G6PD deficiency is usually asymptomatic, however, deficient individuals are at increased risk of developing acute hemolytic anemia and hyperbilirubinemia following intake of oxidative agents and fava. The objective of present study was to detect prevalence of G6PD deficiency in admitted males for premarriage tests in Zahedan Reference Laboratory. Also, we compared blood indices of normal and G6PD deficient individuals.Materials and Methods: This descriptive study was carried out on 1340 admitted males in Zahedan Reference Laboratory from February 2008 to March 2009. G6PD activity was determined in EDTA containing blood samples by qualitative fluorescence spot test, then G6PD deficiency was confirmed by quantitative spectrophotometric method. Total leukocyte count and RBC indices of G6PD deficient samples and the same number of normal samples were compared. The differences between two groups were compared using Sigmaplot software and t-Student test. A P-value less than 0.05 was considered statistically significant.Results: G6PD deficiency was found in 84 individuals of total 1340 by fluorescence spot test and confirmed in 79 by quantitative method. Therefore, prevalence of G6PD deficiency in Zahedan was estimated to be 5.9%. Comparison of deficient and normal individuals did not show significant difference in WBC count, RBC count, hemoglobin concentration, hematocrit, mean corpuscular hemoglobin (MCH and RDW-SD. However, mean corpuscular volume (MCV was significantly high and mean corpuscular hemoglobin concentration (MCHC and RDW-CV were significantly low in G6PD deficient individuals compared to those with normal enzyme level.Discussion: Present study revealed that the prevalence of G6PD deficiency in Zahedan is 5.9%. Severity of G6PD deficiency in quantitative assay indicated that class I and II are probably dominant variants in

  17. STUDY OF GLUCOSE 6-PHOSPHATE DEHYDROGENASE (G6PD DEFICIENCY IN JAUNDICED NEONATES OF A TERTIARY CARE CENTRE OF NORTH-EAST INDIA

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    Aukifa Khamim

    2016-05-01

    Full Text Available roteins from oxidative damage. Glucose-6-Phosphate Dehydrogenase (G6PD deficiency is the commonest red cell enzyme abnormality associated with haemolysis leading to Neonatal Jaundice (NNJ. It is a genetically inherited X-linked abnormality. AIMS To find out incidence of G6PD deficiency amongst jaundiced patients and relation between G6PD deficiency and sex, peak level of Total Serum Bilirubin (TSB, significant hyperbilirubinemia, duration of phototherapy and need for exchange transfusion. SETTINGS AND DESIGN Hospital based retrospective study. METHODS AND MATERIALS This retrospective study was carried out among 1224 jaundiced neonates needing phototherapy admitted in the Neonatology Unit of Dept. of Paediatrics (March 2015 to October 2015, Assam Medical College and Hospital (AMCH, Dibrugarh, Assam. STATISTICAL ANALYSIS USED Data were entered in SPSS (Software package for statistical analysis, version 16 and analysed using Chi-Square test and Mann Whitney U test. RESULTS A total of 2574 neonates were admitted during the 8 months period, of which 1224 had NNJ (47.5%. Of these 77 (5.07% babies were G6PD deficient. Male (n=53 to female (n=24 ratio was 2:1. The commonest age at presentation was 2nd to 4th days in both G6PD deficient and G6PD normal neonates. Mean peak-TSB level in G6PD deficient cases (20.03±5.30 mg/dL was significantly higher than G6PD normal cases (16.67±3.93 mg/dL; 45% of G6PD deficient neonates developed significant hyperbilirubinemia (Indirect bilirubin more than 20 mg% and required Double Volume Exchange Transfusion (DVET. Mean duration of phototherapy in G6PD deficient NNJ babies is 2.5±1.2 days, which is significantly higher (p<0.05 when compared to G6PD normal NNJ babies where it is 2±1.1 days. In babies with significant hyperbilirubinemia, it is seen that there is signif icant difference (p<0.001 between G6PD deficient and G6PD normal babies. There was significant difference in requirement of DVET between G6PD deficient

  18. First evaluation of glucose-6-phosphate dehydrogenase (G6PD deficiency in vivax malaria endemic regions in the Republic of Korea.

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    Youn-Kyoung Goo

    Full Text Available BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common human enzyme defect and affects more than 400 million people worldwide. This deficiency is believed to protect against malaria because its global distribution is similar. However, this genetic disorder may be associated with potential hemolytic anemia after treatment with anti-malarials, primaquine or other 8-aminoquinolines. Although primaquine is used for malaria prevention, no study has previously investigated the prevalence of G6PD variants and G6PD deficiency in the Republic of Korea (ROK. METHODS: Two commercialized test kits (Trinity G-6-PDH and CareStart G6PD test were used for G6PD deficiency screening. The seven common G6PD variants were investigated by DiaPlexC kit in blood samples obtained living in vivax malaria endemic regions in the ROK. RESULTS: Of 1,044 blood samples tested using the CareStart G6PD test, none were positive for G6PD deficiency. However, a slightly elevated level of G6PD activity was observed in 14 of 1,031 samples tested with the Trinity G-6-PDH test. Forty-nine of the 298 samples with non-specific amplification by DiaPlexC kit were confirmed by sequencing to be negative for the G6PD variants. CONCLUSIONS: No G6PD deficiency was observed using phenotypic- or genetic-based tests in individuals residing in vivax malaria endemic regions in the ROK. Because massive chemoprophylaxis using primaquine has been performed in the ROK military to kill hypnozoites responsible for relapse and latent stage vivax malaria, further regular monitoring is essential for the safe administration of primaquine.

  19. Dissimilar Deficiency of Glucose-6-Phosphate Dehydrogenase (G-6-PD) among the AFARS and the Somalis of Djibouti

    Science.gov (United States)

    1991-01-01

    directly related to the type ot variant Plus de 200 variantes de la moliculc G-6-PD present. ont it dicrites i ce jour, (1) Medical Research Assistant...Research Associate, International Health Program, School of Medicine, University of Maryland. Baltimore. MEDECINE TROPICALE - Volume 51 - IN’ 2 - Avni - Juin...hemolytiques severes qui semblent relativementfriquentes i Djibouti chez les malades awc himaties parasities accis palustres (MIARY, Uniti de Soins Intensifs

  20. Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Ouest and Sud-Est departments of Haiti.

    Science.gov (United States)

    von Fricken, Michael E; Weppelmann, Thomas A; Eaton, Will T; Alam, Meer T; Carter, Tamar E; Schick, Laura; Masse, Roseline; Romain, Jean R; Okech, Bernard A

    2014-07-01

    Malaria remains a significant public health issue in Haiti, with chloroquine (CQ) used almost exclusively for the treatment of uncomplicated infections. Recently, single dose primaquine (PQ) was added to the Haitian national malaria treatment policy, despite a lack of information on the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency within the population. G6PD deficient individuals who take PQ are at risk of developing drug induced hemolysis (DIH). In this first study to examine G6PD deficiency rates in Haiti, 22.8% (range 14.9%-24.7%) of participants were found to be G6PD deficient (class I, II, or III) with 2.0% (16/800) of participants having severe deficiency (class I and II). Differences in deficiency were observed by gender, with males having a much higher prevalence of severe deficiency (4.3% vs. 0.4%) compared to females. Male participants were 1.6 times more likely to be classified as deficient and 10.6 times more likely to be classified as severely deficient compared to females, as expected. Finally, 10.6% (85/800) of the participants were considered to be at risk for DIH. Males also had much higher rates than females (19.3% vs. 4.6%) with 4.9 times greater likelihood (p value 0.000) of having an activity level that could lead to DIH. These findings provide useful information to policymakers and clinicians who are responsible for the implementation of PQ to control and manage malaria in Haiti. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. DNA damage and apoptosis in mononuclear cells from glucose-6-phosphate dehydrogenase-deficient patients (G6PD Aachen variant) after UV irradiation.

    Science.gov (United States)

    Efferth, T; Fabry, U; Osieka, R

    2001-03-01

    Patients affected with X chromosome-linked, hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency suffer from life-threatening hemolytic crises after intake of certain drugs or foods. G6PD deficiency is associated with low levels of reduced glutathione. We analyzed mononuclear white blood cells (MNC) of three males suffering from the German G6PD Aachen variant, four heterozygote females of this family, one G6PD-deficient male from another family coming from Iran, and six healthy male volunteers with respect to their DNA damage in two different genes (G6PD and T-cell receptor-delta) and their propensity to enter apoptosis after UV illumination (0.08-5.28 J/cm2). As determined by PCR stop assays, there was more UV-induced DNA damage in MNC of G6PD-deficient male patients than in those of healthy subjects. MNC of G6PD-deficient patients showed a higher rate of apoptosis after UV irradiation than MNC of healthy donors. MNC of heterozygote females showed intermediate rates of DNA damage and apoptosis. It is concluded that increased DNA damage may be a result of deficient detoxification of reactive oxygen species by glutathione and may ultimately account for the higher rate of apoptosis in G6PD-deficient MNC.

  2. G6PD deficiency at Sumba in Eastern Indonesia is prevalent, diverse and severe: implications for primaquine therapy against relapsing Vivax malaria.

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    Ari Winasti Satyagraha

    2015-03-01

    Full Text Available Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1% were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb. The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001, and 6.7% and 3.1% for G6PD deficiency (P<0.001 at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm.

  3. Evaluation of the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT in a malaria endemic area in Ghana, Africa.

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    Dennis Adu-Gyasi

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most widespread enzyme defect that can result in red cell breakdown under oxidative stress when exposed to certain medicines including antimalarials. We evaluated the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT as a point-of-care tool for screening G6PD deficiency.A cross-sectional study was conducted among 206 randomly selected and consented participants from a group with known G6PD deficiency status between February 2013 and June 2013. A maximum of 1.6ml of capillary blood samples were used for G6PD deficiency screening using CareStart G6PD RDT and Trinity qualitative with Trinity quantitative methods as the "gold standard". Samples were also screened for the presence of malaria parasites. Data entry and analysis were done using Microsoft Access 2010 and Stata Software version 12. Kintampo Health Research Centre Institutional Ethics Committee granted ethical approval.The sensitivity (SE and specificity (SP of CareStart G6PD deficiency RDT was 100% and 72.1% compared to Trinity quantitative method respectively and was 98.9% and 96.2% compared to Trinity qualitative method. Malaria infection status had no significant (P=0.199 change on the performance of the G6PD RDT test kit compared to the "gold standard".The outcome of this study suggests that the diagnostic performance of the CareStart G6PD deficiency RDT kit was high and it is acceptable at determining the G6PD deficiency status in a high malaria endemic area in Ghana. The RDT kit presents as an attractive tool for point-of-care G6PD deficiency for rapid testing in areas with high temperatures and less expertise. The CareStart G6PD deficiency RDT kit could be used to screen malaria patients before administration of the fixed dose primaquine with artemisinin-based combination therapy.

  4. Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

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    Swanson, Nancy L.; Li, Chen

    2016-01-01

    Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA's Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren's syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process.

  5. Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

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    Stephanie Seneff

    2016-01-01

    Full Text Available Osteonecrosis of the jaw (ONJ, a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA’s Adverse Event Reporting System (FAERS provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren’s syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process.

  6. A novel mis-sense mutation (G1381A) in the G6PD gene identified in a Chinese man

    Institute of Scientific and Technical Information of China (English)

    任晓琴; 杜传书; 蒋玮莹; 陈路明; 林群娣; 何永蜀

    2001-01-01

    目的对中国云南省29例G6PD缺乏症患者检查新的基因突变型。 方法用NBT法作G6PD缺乏症筛查、SSCP、ACRS和DNA测序鉴定突变。结果29例中发现G1388A18例、C1004A1例、G1381A1例,另外9例未定型。其中1381突变为新的错义 突变。这一突变导致G6PD丙氨酸被苏氨酸置换(A461T),并导致一天然StuI酶切位点的消失,此特点可 用于该突变的鉴定。 结论我们发现一新的错义突变。此突变导致丙氨酸被苏氨酸置换(A461T),且此突变对酶活性降低是 重要的。%Objective To detect new mutations among 29 glucose-6-phosphatedehydrogenase (G6PD) deficient individuals from Yunnan province. Methods The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. Results Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. Conclusion A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation.

  7. Performance of the CareStart™ G6PD Deficiency Screening Test, a Point-of-Care Diagnostic for Primaquine Therapy Screening

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    Kim, Saorin; Nguon, Chea; Guillard, Bertrand; Duong, Socheat; Chy, Sophy; Sum, Sarorn; Nhem, Sina; Bouchier, Christiane; Tichit, Magali; Christophel, Eva; Taylor, Walter R. J.; Baird, John Kevin; Menard, Didier

    2011-01-01

    Development of reliable, easy-to-use, rapid diagnostic tests (RDTs) to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency at point of care is essential to deploying primaquine therapies as part of malaria elimination strategies. We assessed a kit under research and development called CareStart™ G6PD deficiency screening test (Access Bio, New Jersey, USA) by comparing its performance to quantitative G6PD enzyme activity using a standardized spectrophotometric method (‘gold standard’). Blood samples (n = 903) were collected from Cambodian adults living in Pailin province, western Cambodia. G6PD enzyme activities ranged from 0 to 20.5 U/g Hb (median 12.0 U/g Hg). Based on a normal haemoglobin concentration and wild-type G6PD gene, the normal values of G6PD enzymatic activity for this population was 3.6 to 20.5 U/g Hg (95th percentiles from 5.5 to 17.2 U/g Hg). Ninety-seven subjects (10.7%) had <3.6 U/g Hg and were classified as G6PD deficient. Prevalence of deficiency was 15.0% (64/425) among men and 6.9% (33/478) among women. Genotype was analyzed in 66 G6PD-deficient subjects and 63 of these exhibited findings consistent with Viangchang genotype. The sensitivity and specificity of the CareStart™ G6PD deficiency screening test was 0.68 and 1.0, respectively. Its detection threshold was <2.7 U/g Hg, well within the range of moderate and severe enzyme deficiencies. Thirteen subjects (1.4%, 12 males and 1 female) with G6PD enzyme activities <2 U/g Hg were falsely classified as “normal” by RDT. This experimental RDT test here evaluated outside of the laboratory for the first time shows real promise, but safe application of it will require lower rates of falsely “normal” results. PMID:22164279

  8. Molecular Heterogeneity of Glucose-6-Phosphate Dehydrogenase Deficiency in Burkina Faso: G-6-PD Betica Selma and Santamaria in People with Symptomatic Malaria in Ouagadougou

    Science.gov (United States)

    Ouattara, Abdoul Karim; Yameogo, Pouiré; Diarra, Birama; Obiri-Yeboah, Dorcas; Yonli, Albert; Compaore, Tegwindé Rebeca; Soubeiga, Serge Théophile; Djigma, Florencia Wenkuuni; Simpore, Jacques

    2016-01-01

    The G-6-PD deficiency has an important polymorphism with genotypic variants such as 202A/376G, 376G/542T and 376G/968T known in West African populations. It would confer protection against severe forms of malaria although there are differences between the various associations in different studies. In this study we genotyped six (06) variants of the G-6-PD gene in people with symptomatic malaria in urban areas in Burkina Faso. One hundred and eighty-two (182) patients who tested positive using rapid detection test and microscopy were included in this study. A regular PCR with the GENESPARK G6PD African kit was run followed by electrophoresis, allowing initially to genotype six SNPs (G202A, A376G, A542T, G680T, C563T and T968C). Women carrying the mutations 202A and/or 376G were further typed by real-time PCR using TaqMan probes rs1050828 and rs1050829. In the study population the G-6-PD deficiency prevalence was 9.9%. In addition of G-6-PD A- (202A/376G) variant, 376G/542T and 376G/968T variants were also detected. Hemoglobin electrophoresis revealed that 22.5% (41/182) of the individuals had HbAC compared with2.2% with HbAS and one individual had double heterozygous HbSC. There was no correlation between the G-6-PD deficiency or haemoglobinopathies and symptomatic malaria infections in this study. Our study confirms that the G-6-PD deficiency does not confer protection against Plasmodium falciparum infections. As opposed to previous genotyping studies carried out in Burkina Faso, this study shows for the first time the presence of the variant A- (376G/968C) and warrants further investigation at the national level and in specific ethnic groups. PMID:27413522

  9. Glucose-6-phosphate dehydrogenase(G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso

    Institute of Scientific and Technical Information of China (English)

    Abdoul; Karim; Ouattara; Cyrille; Bisseye; Bapio; Valery; Jean; Télesphore; Elvira; Bazie; Birama; Diarra; Tegwindé; Rebeca; Compaore; Florencia; Djigma; Virginio; Pietra; Remy; Moret; Jacques; Simpore

    2014-01-01

    Objective:To investigate 4 combinations of mutations responsible for glucose-6—phosphate dehydrogenase(G6PD) deficiency in a rural community of Burkina Faso,a malaria endemic country.Methods:Two hundred individuals in a rural community were genotyped for the mutations A376 G.G202A,A542 T,G680T and T968 C using TaqMan single nucleotide polymorphism assays and polymerase chain reaction followed by restriction fragment length polymorphism.Results:The prevalence of the G6 PD deficiency was 9.5%,in the study population.It was significantly higher in men compared to women(14.23%vs 6.0%,P=0.049).The 202A/376 G G6PD Awas the only deficient variant detected.Plasmodium falciparum asymptomatic parasitemia was significantly higher among the C6PD-non—deficient persons compared to the G6PD-deficient(P<0.001).The asymptomatic parasitemia was also significantly higher among G(SPI) nondeficient compared to C6PD—heterozygous females(P<0.001).Conclusions:This study showed that the G6 PD A- variant associated with protection against asymptomatic malaria in Burkina Faso is probably the most common deficient variant.

  10. The use of primaquine in malaria infected patients with red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency in Myanmar.

    Science.gov (United States)

    Myat-Phone-Kyaw; Myint-Oo; Aung-Naing; Aye-Lwin-Htwe

    1994-12-01

    32 subjects with Plasmodium falciparum gametocytes, and 31 cases with Plasmodium vivax infection from two military hospitals (Lashio, Mandalay) were treated with quinine 600 mg three times a day for 7 days followed by primaquine 45 mg single dose for gametocytes and 45 mg weekly x 8 weeks for vivax malaria. Although screening of red cell glucose-6-phosphate dehydrogenase (G6PD) was done prior to primaquine treatment, G6PD deficient subjects were not excluded from the trial. 20 patients hemizygous for mild G6PD deficiency (GdB- variant), 2 patients hemizygous for severe deficiency (Gd-Myanmar variant) completed the trial. No case of acute hemolysis was observed in all 22 patients with two genotypes of red cell G6PD deficiency status. Therefore, a single dose of primaquine 45 mg and/or weekly for 8 weeks is adequate for the treatment of patients with P. falciparum gametocytes and/or P. vivax malaria ignoring these red cell G6PD enzyme deficient variants in Myanmar.

  11. Diospyros lotus L. fruit extract protects G6PD-deficient erythrocytes from hemolytic injury in vitro and in vivo: prevention of favism disorder.

    Science.gov (United States)

    Azadbakht, M; Hosseinimehr, S J; Shokrzadeh, M; Habibi, E; Ahmadi, A

    2011-11-01

    The aim of this study was to evaluate the protective effect of Diospyros lotus L. fruit extract against the hemolytic damage induced by Vicia faba beans extract in both G6PD enzyme-deficient human and rat erythrocyte in vitro and in vivo. In the former model, venous blood samples were obtained from five subjects with known G6PD deficiency and erythrocyte hemolysis induced by Vicia faba L. bean extract was asessed spectrophotometrically in the presence and absence of Diospyros lotus L. fruits extract. In the in vivo model, G6PD-deficient rats (induced by intraperitoneal injection of dehydroepiandrosterone for 35 days) pre-treated with different doses of Diospyros lotus L. (500, 750, 1000, and 1500 mg/kg, p.o for 7 days) were challenged with Vicia faba beans extract and the protective effect of the fruit extract against hemolysis was evaluated as above. The results have shown that Diospyros lotus L. fruits extract has antioxidant activity that may protect against hemolytic damage induced by Vicia faba bean extract in both G6PD-deficient human and rat erythrocytes. The study gives a scientific basis for the efficacy of the fruit extract as used in Iran. The fact that this was shown in human erythrocytes in vitro is significant and provides a rationale for further testing in vivo in G6PD-deficient human populations.

  12. Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens

    Science.gov (United States)

    Win, Htun Htun; Thitipanawan, Niramon; Po, Christina; Chowwiwat, Nongnud; Raksapraidee, Rattanaporn; Wilairisak, Pornpimon; Keereecharoen, Lily; Proux, Stéphane

    2017-01-01

    Background Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD “normal” by current phenotypic screening tests. Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized. Methods and Findings In a cohort study nested within a randomised clinical trial that compared different treatment regimens for P. vivax malaria, patients with a normal standard NADPH fluorescent spot test result (≳30%–40% of normal G6PD activity) were randomised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine, either the standard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants. Between 21 February 2012 and 04 July 2014, 241 female participants were enrolled, of whom 34 were heterozygous for the G6PD Mahidol variant. Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinically significant haemolysis (fractional haematocrit reduction >25%) in G6PD heterozygotes taking the higher (7 d) primaquine dose (9/17 [53%]) compared with G6PD heterozygotes taking the standard high (14 d) dose (2/16 [13%]; p = 0.022). In heterozygotes, the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose (7-d regimen): −20.4% (95% CI −26.0% to −14.8%) (nadir on day 5) compared with the standard high (14 d) dose: −13.1% (95% CI −17.6% to −8.6%) (nadir day 6). Two heterozygotes taking the higher (7 d) primaquine dose

  13. The impact of phenotypic and genotypic G6PD deficiency on risk of plasmodium vivax infection: a case-control study amongst Afghan refugees in Pakistan.

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    Toby Leslie

    2010-05-01

    Full Text Available BACKGROUND: The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A- G6PD (glucose-6-phosphate dehydrogenase deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine. If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection. METHODS AND FINDINGS: A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI 0.06-0.52], p = 0.001. Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02-0.92], p = 0.041. The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15-0.94], p = 0.037. CONCLUSIONS: G6PD deficiency (Mediterranean type conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human

  14. Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.

    Science.gov (United States)

    Peixoto, Henry Maia; Brito, Marcelo Augusto Mota; Romero, Gustavo Adolfo Sierra; Monteiro, Wuelton Marcelo; de Lacerda, Marcus Vinícius Guimarães; de Oliveira, Maria Regina Fernandes

    2017-01-01

    The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon. © 2016 John Wiley & Sons Ltd.

  15. Using G6PD tests to enable the safe treatment of Plasmodium vivax infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis.

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    Angela Devine

    2017-05-01

    Full Text Available Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings.Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1 giving chloroquine alone and (2 giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar.In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values

  16. Using G6PD tests to enable the safe treatment of Plasmodium vivax infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis.

    Science.gov (United States)

    Devine, Angela; Parmiter, Minnie; Chu, Cindy S; Bancone, Germana; Nosten, François; Price, Ric N; Lubell, Yoel; Yeung, Shunmay

    2017-05-01

    Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs) offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings. Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs) associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1) giving chloroquine alone and (2) giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar. In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values, including the

  17. Validation of the rapid test Carestart(tm G6PD among malaria vivax-infected subjects in the Brazilian Amazon

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    Marcelo Augusto Mota Brito

    Full Text Available Abstract: INTRODUCTION: In the Brazilian Amazon, malaria infections are primarily caused by Plasmodium vivax. The only drug that kills the hypnozoite form of P. vivax is primaquine, thereby preventing relapse. However, treating glucose-6-phosphate dehydrogenase (G6PD-deficient individuals with primaquine can lead to severe hemolysis. G6PD deficiency (G6PDd affects approximately 400 million people worldwide, most of whom live in malaria-endemic areas. Therefore, clinicians need tools that can easily and reliably identify individuals with G6PDd. This study estimated the accuracy of the Carestart(tm G6PD rapid test (Access Bio in the diagnosis of G6PDd in male participants with and without P. vivax acute malaria. METHODS: Male participants were recruited in Manaus. Malaria diagnosis was determined by thick blood smear. G6PD quantitative analysis was performed spectro photometrically at a wave length of 340nm. The Carestart(tm G6PD test was performed using venous blood. Genotyping was performed for individuals whose samples had an enzyme activity less than 70% of the normal value. RESULTS: Six hundred and seventy-four male participants were included in this study, of whom 320 had a diagnosis of P. vivax malaria. In individuals with enzyme activity lower than 30% (n=13, the sensitivity, specificity, positive predictive value, and negative predictive value of the Carestart(tm G6PD test were as follows: 61.5% (95%CI: 35.5%-82.3%, 98.3% (95%CI: 97.0%-99.1%, 42.1% (95%CI: 23.1%-63.7%, and 99.2% (95%CI: 98.2%-82.3%, 98.3% (95%CI: 97.0%-99.1%, 42.1% (95%CI: 23.1%-63.7%, and 99.2% (95%CI: 98.2%-99.7%, respectively. Increases in sensitivity were observed when increasing the cut-off value. CONCLUSIONS: Despite low sensitivity, Carestart(tm G6PD remains a good alternative for rapid diagnosis of G6PDd in malaria-endemic regions.

  18. Heterogeneity of G6PD deficiency prevalence in Mozambique: a school-based cross-sectional survey in three different regions.

    Science.gov (United States)

    Galatas, Beatriz; Mabote, Lurdes; Simone, Wilson; Matambisso, Gloria; Nhamussua, Lidia; Mañú-Pereira, María Del Mar; Menéndez, Clara; Saute, Francisco; Macete, Eusebio; Bassat, Quique; Alonso, Pedro; Aide, Pedro

    2017-01-19

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary enzymatic abnormality that affects more than 400 million people worldwide. Most deficient individuals do not manifest any symptoms; however, several precipitant agents-such as fava intake, infections, or several drugs-may trigger acute haemolytic anaemia. Countries should be informed of the prevalence of this enzymatic anomaly within their borders, in order to make safe and appropriate national decisions regarding the use of potentially unsafe drugs for G6PD deficient individuals. A school-based cross-sectional survey was conducted in three districts in Mozambique, namely Manhiça, located in the south; Mocuba in the centre; and Pemba in the northern tip of the country. G6PD deficiency was evaluated using the CareStart™ diagnostic test, and enzyme activity levels were measured through fluorescence spectrophotometry in deficient individuals. Chi squared and ANOVA tests were used to assess prevalence and mean enzyme activity differences, and logistic regression was used to identify risk factors associated to the deficiency. G6PD deficiency prevalence estimates were lowest in the northern city of Pemba (8.3%) and among Emakhuwas and Shimakondes, and higher in the centre and southern regions of the country (16.8 and 14.6%, respectively), particularly among Elomwes and Xichanganas. G6PD deficiency was significantly more prevalent among male students than females (OR = 1.4, 95% CI 1.0-1.8, p = 0.02), although enzyme activity levels were not different among deficient individuals from either gender group. Finally, median deficiency levels were found to be more severe among the deficient students from the north (0.7 U/gHg [0.2-0.7] p < 0.001) and south (0.7 U/gHg [0.5-2.5]), compared to those from the centre (1.4 U/gHg [0.6-2.1]). These findings suggest that Mozambique, as a historically high malaria-endemic country has considerable levels of G6PD deficiency, that vary significantly

  19. Glucose-6-phosphate dehydrogenase (G6PD. Response of the human erythrocyte and another cells to the decrease in their activity.

    Directory of Open Access Journals (Sweden)

    Javier Fernando Bonilla

    2009-11-01

    Full Text Available Glucose-6-phosphate dehydrogenase is the first enzyme in the pentose phosphate pathway and the main intracellular source of reduced nicotidamineadenine nucleotidephosphate (NADPH, involved in diverse physiological processes such as antioxidant defense, (for instance in the erythrocyte endothelial growth modulation, erithropoyesis, vascularization and phagocitosis. G6PDH deficiency is the most common X-chromosome-linked enzymopathy in human beings. Although it is present in any type cell, its absolute deficiency is incompatible with life. According to WHO, 400 million people are affected by G6PD deficiency in the world but in Colombia, the severe form prevalence is about 3% to 7%. There are no data related to slight and moderate alterations, that also have clinical effects. This paper reviews some G6PD biomolecular aspects, its classification according to activity and electrophoretic mobility, as well as some main clinical aspects related to its activity alteration.

  20. Investigação genético-epidemiológica e molecular da deficiência de G-6-PD em uma comunidade brasileira

    Directory of Open Access Journals (Sweden)

    Mariane B. Compri

    2000-06-01

    Full Text Available Este trabalho teve por objetivo estudar a deficiência de G-6-PD em uma comunidade do interior do Estado de São Paulo (Bragança Paulista. Durante 36 meses foram selecionados 4.621 doadores de sangue do sexo masculino, detectando-se 80 deficientes em G-6-PD. A análise molecular foi realizada em 70 deficientes não consangüíneos mediante a amplificação de DNA por PCR seguida de digestão por enzimas de restrição e análise de polimorfismo de conformação em hélice simples (SSCP. Em 98,6% dos casos, foi identificada a mutação G-6-PD A- (202 G->A, por digestão do exon 4 com Nla III. Verificou-se a presença de mutação mais rara no exon 9, por SSCP. Não foi constatado caso da variante Mediterrânea. Tais resultados mostraram que a variante A- (202 G->A, quase que exclusiva, foi introduzida na comunidade não apenas por descendentes de africanos, como também pelos imigrantes italianos, espanhóis e portugueses. A contribuição italiana em termos da variante Mediterrânea de G-6-PD foi menor do que a sua participação em termos de talassemia beta, provavelmente devido à origem no Norte da Itália.

  1. Investigação genético-epidemiológica e molecular da deficiência de G-6-PD em uma comunidade brasileira

    Directory of Open Access Journals (Sweden)

    Compri Mariane B.

    2000-01-01

    Full Text Available Este trabalho teve por objetivo estudar a deficiência de G-6-PD em uma comunidade do interior do Estado de São Paulo (Bragança Paulista. Durante 36 meses foram selecionados 4.621 doadores de sangue do sexo masculino, detectando-se 80 deficientes em G-6-PD. A análise molecular foi realizada em 70 deficientes não consangüíneos mediante a amplificação de DNA por PCR seguida de digestão por enzimas de restrição e análise de polimorfismo de conformação em hélice simples (SSCP. Em 98,6% dos casos, foi identificada a mutação G-6-PD A- (202 G->A, por digestão do exon 4 com Nla III. Verificou-se a presença de mutação mais rara no exon 9, por SSCP. Não foi constatado caso da variante Mediterrânea. Tais resultados mostraram que a variante A- (202 G->A, quase que exclusiva, foi introduzida na comunidade não apenas por descendentes de africanos, como também pelos imigrantes italianos, espanhóis e portugueses. A contribuição italiana em termos da variante Mediterrânea de G-6-PD foi menor do que a sua participação em termos de talassemia beta, provavelmente devido à origem no Norte da Itália.

  2. Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells.

    Science.gov (United States)

    Wang, Xiaolin; Wu, Guang; Cao, Guangxin; Yang, Lei; Xu, Haifei; Huang, Jian; Hou, Jianquan

    2015-09-01

    Zoledronic acid (ZA) is the current standard of care for the therapy of patients with bone metastasis or osteoporosis. ZA inhibits the prenylation of small guanosine‑5'-triphosphate (GTP)‑binding proteins, such as Ras, and thus inhibit Ras signaling. The present study demonstrated that ZA inhibited cell proliferation and the pentose phosphate pathway (PPP) in bladder cancer cells. In addition, the expression of glucose‑6‑phosphate dehydrogenase (G6PD, the rate‑limiting enzyme of the PPP) was found to be inhibited by ZA. Furthermore, the stability of TAp73, which activates the expression G6PD was decreased in zoledronic acid treated cells. Decreased levels of Ras‑GTP and phosphorylated‑extracellular signal-regulated kinase 1/2 were also observed following treatment with ZA. This may be due to the fact that activated Ras was reported to stabilize TAp73 inducing its accumulation. The inhibition of Ras activity by PT inhibitor II also significantly reduced the levels of TAp73 and G6PD and the PPP flux. Moreover, knockdown of TAp73, attenuated the PPP flux and eliminated the affection of ZA on the PPP flux. In conclusion, it was proposed that ZA can inhibit stability of TAp73 and attenuate the PPP via blocking Ras signaling in bladder cancer cells.

  3. Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study

    Directory of Open Access Journals (Sweden)

    Hanae Shimo

    2011-01-01

    Full Text Available It is well known that G6PD-deficient individuals are highly susceptible to oxidative stress. However, the differences in the degree of metabolic alterations among patients during an oxidative crisis have not been extensively studied. In this study, we applied mathematical modeling to assess the metabolic changes in erythrocytes of various G6PD-deficient patients during hydrogen peroxide- (H2O2- induced perturbation and predict the kinetic properties that elicit redox imbalance after exposure to an oxidative agent. Simulation results showed a discrepancy in the ability to restore regular metabolite levels and redox homeostasis among patients. Two trends were observed in the response of redox status (GSH/GSSG to oxidative stress, a mild decrease associated with slow recovery and a drastic decline associated with rapid recovery. The former was concluded to apply to patients with severe clinical symptoms. Low max and high mG6P of G6PD were shown to be kinetic properties that enhance consequent redox imbalance.

  4. Investigation of Cosenza Mutation in Patients with Deficiency of Glucose-6-Phosphate Dehydrogenase (G6PD in North West of Iran

    Directory of Open Access Journals (Sweden)

    Omolbanin Javadi

    2015-03-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is a greatly polymorphic enzyme encoded by human X-linked gene. G6PD deficit is the most public enzymopathy in human with about 400 million people affected globally. It is the main controlling enzyme in the hexose monophosphate shunt catalase the oxidation of glucose-6-phosphate  to 6-phosphogluconolacton and the creation of reducing equals in the form of NADPH to meet the cellular redox formal and its absence origin hemolytic anemia - favism and newborn jaundice. Mutation in this enzyme cause three major types of unusual phenotype, including Mediterranean, Chatham and Cosenza. In this study, by Rapid Genomic DNA Extraction (RGDE method, from 90 blood samples of unrelated male and female patients with genetic deficiency of G6PD, DNA was removed and next digestion by Eco81I enzymes, in order to research for Cosenza mutation, they were analyzed by means of PCR-RFLP. Sequencing methods were used. Of 90 patients, one patient had a Cosenza mutation frequency of 1.01%. Eighty-nine patients (98.99% were not affected by the Cosenza-type mutation. Accordingly, Cosenza mutation is not regarded as the most common mutation in Iranian North-west population.   

  5. Investigation of Cosenza Mutation in Patients with Deficiency of Glucose-6-Phosphate Dehydrogenase (G6PD in North West of Iran

    Directory of Open Access Journals (Sweden)

    Omolbanin Javadi Javadi

    2015-02-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is a greatly polymorphic enzyme encoded by human X-linked gene. G6PD deficit is the most public enzymopathy in human with about 400 million people affected globally. It is the main controlling enzyme in the hexose monophosphate shunt catalase the oxidation of glucose-6-phosphate  to 6-phosphogluconolacton and the creation of reducing equals in the form of NADPH to meet the cellular redox formal and its absence origin hemolytic anemia - favism and newborn jaundice. Mutation in this enzyme cause three major types of unusual phenotype, including Mediterranean, Chatham and Cosenza. In this study, by Rapid Genomic DNA Extraction (RGDE method, from 90 blood samples of unrelated male and female patients with genetic deficiency of G6PD, DNA was removed and next digestion by Eco81I enzymes, in order to research for Cosenza mutation, they were analyzed by means of PCR-RFLP. Sequencing methods were used. Of 90 patients, one patient had a Cosenza mutation frequency of 1.01%. Eighty-nine patients (98.99% were not affected by the Cosenza-type mutation. Accordingly, Cosenza mutation is not regarded as the most common mutation in Iranian North-west population.   

  6. Molecular identification of Gd A- and Gd B- G6PD deficient variants by ARMS-PCR in a Tunisian population.

    Science.gov (United States)

    Haloui, Sabrine; Laouini, Naouel; Sahli, Chaima Abdelhafidh; Daboubi, Rim; Becher, Mariem; Jouini, Latifa; Kazdaghli, Kalthoum; Tinsa, Faten; Cherif, Semia; Khemiri, Monia; Fredj, Sondess Hadj; Othmani, Rim; Ouali, Faida; Siala, Hajer; Toumi, Nour El Houda; Barsaoui, Sihem; Bibi, Amina; Messaoud, Taieb

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy. More than 200 mutations in the G6PD gene have been described. In Tunisia, the A-African and the B-Mediterranean mutations predominate the mutational spectrum. The purpose of this study was to apply the amplification refractory mutation system (ARMS-PCR) to the identification of Gd A+, Gd A- and Gd B- variants in a cohort of deficient individuals and to establish a phenotype/genotype association. 90 subjects were screened for enzymatic deficiency by spectrophotometric assay. The molecular analyses were performed in a group of 50 unrelated patients. Of the 54 altered chromosomes examined, 60% had the Gd A- mutation, 18% showed the Gd B- mutation and in 20% of cases, no mutations have been identified. The ARMS-PCR showed complete concordance with the endonuclease cleavage reference method and agreed perfectly with previous Tunisian studies where Gd A- and Gd B- were the most encountered. Also, similarities in spectrum mutations with North African and Mediterranean countries suggest gene migration from Africa to Europe through Spain. In conclusion, ARMS has been introduced in this study for common G6PD alleles identification in Tunisia. It gives some advantages compared to the traditional endonuclease digestion method since it is more convenient and timesaving and also offers the possibility to be applied in mass screening surveys.

  7. Correlation of G6PD activity and thalassemia%G6PD活性与地中海贫血的相关性研究

    Institute of Scientific and Technical Information of China (English)

    黄佐荣; 苏国生

    2014-01-01

    Objective To investigate the G6PD activity correlated with thalassemia. Methods automatic biochemical analyzer patients with G6PD activity on quantitative analysis, thalassemia screening using automated hemoglobin electrophoresis analysis system, and abnormal results of patient samples for genotyping confirmed.Results 3626 cases studied, there are 652 cases of G6PD activity increased, and G6PD activity in patients with elevated hemoglobin electrophoresis test results significantly improve the chances of abnormalities, confirmed by genotyping, mild positive rate of α-thalassemia to 25.92%, light β thalassemia positive rate was 34.97%, heavy β thalassemia positive rate was 1.53%, thalassemia positive rate was 62.42% of the total, with normal G6PD activity thalassemia total positive rate comparison, χ2= 817.42, P=0.0008, a statistical y significant difference. Conclusion G6PD activity is higher, the greater the risk the chance of thalassemia, G6PD activity in patients considered for screening, clinical diagnosis can help thalassemia.%目的:探讨G6PD活性与地中海贫血的相关性。方法采用全自动生化仪对患者进行G6PD活性定量分析,用全自动血红蛋白分析系统进行地中海贫血筛查,并对异常结果患者标本进行基因分型确诊。结果在3626例研究对象中,有652例G6P D活性升高,而G6P D活性升高的患者血红蛋白电泳检测结果异常的几率明显提高,经基因分型确证,轻度α地中海贫血阳性检出率为25.92%,轻型β地中海贫血阳性检出率为34.97%,重型β地中海贫血阳性检出率为1.53%,地中海贫血总阳性检出率为62.42%,与G6PD活性正常组地中海贫血总阳性检出率比较,χ2=817.42,P=0.0008,差异具有统计学意义。结论 G6PD活性越高,患地中海贫血的几率越大,认为对患者进行G6PD活性筛查,可有助于地中海贫血的临床诊断。

  8. Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Gorlin, J.B. (Brigham and Women' s Hospital, Boston, MA (United States) Dana-Farber Cancer Institute, Boston, MA (United States)); Henske, E.; Hartwig, J.H.; Kwiatkowski, D.J. (Brigham and Women' s Hospital, Boston, MA (United States)); Warren, S.T.; Kunst, C.B. (Emory Univ. School of Medicine, Atlanta, GA (United States)); D' Urso, M.; Palmieri, G. (International Institute of Genetics and Biophysics, Naples, (Italy)); Bruns, G. (Children' s Hospital, Boston, MA (United States))

    1993-08-01

    Actin-binding protein-280 (ABP-280) is a dimeric actin filament-crosslinking protein that promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. The authors have mapped the ABP-280 filamin gene (FLN) to Xq28 by Southern blot analysis of somatic cell hybrid lines, by fluorescence in situ hybridization, and through identification of portions of the FLN gene within cosmids and YACs mapped to Xq28. The FLN gene is found within a 200-kb region centromeric to the G6PD locus and telomeric to DSX52 and the color vision locus. 23 refs., 2 figs.

  9. Investigação genético-epidemiológica e molecular da deficiência de G-6-PD em uma comunidade brasileira G-6-PD deficiency in a Brazilian community: an investigation involving epidemiological genetics and molecular techniques

    Directory of Open Access Journals (Sweden)

    Mariane B. Compri

    2000-06-01

    Full Text Available Este trabalho teve por objetivo estudar a deficiência de G-6-PD em uma comunidade do interior do Estado de São Paulo (Bragança Paulista. Durante 36 meses foram selecionados 4.621 doadores de sangue do sexo masculino, detectando-se 80 deficientes em G-6-PD. A análise molecular foi realizada em 70 deficientes não consangüíneos mediante a amplificação de DNA por PCR seguida de digestão por enzimas de restrição e análise de polimorfismo de conformação em hélice simples (SSCP. Em 98,6% dos casos, foi identificada a mutação G-6-PD A- (202 G->A, por digestão do exon 4 com Nla III. Verificou-se a presença de mutação mais rara no exon 9, por SSCP. Não foi constatado caso da variante Mediterrânea. Tais resultados mostraram que a variante A- (202 G->A, quase que exclusiva, foi introduzida na comunidade não apenas por descendentes de africanos, como também pelos imigrantes italianos, espanhóis e portugueses. A contribuição italiana em termos da variante Mediterrânea de G-6-PD foi menor do que a sua participação em termos de talassemia beta, provavelmente devido à origem no Norte da Itália.This paper reports on a study of the G-6-PD deficiency in Bragança Paulista, São Paulo State, Brazil. A total of 4,621 male blood donors were investigated over a 36-month period. Of these, 80 had the G-6-PD deficiency. Molecular analysis was performed on 70 unrelated G-6-PD deficients through DNA amplification followed by digestion with restriction enzymes and single strand conformation polymorphism analysis (SSCP. In 98.6%, the G-6-PD A- (202 G->A mutation was observed through digestion of exon 4 with Nla III. The presence of an uncommon mutation in exon 9 was also observed through SSCP. No case of the Mediterranean variant was observed. These results indicate that the A- (202G->A variant, almost exclusive, was introduced into the community not only by individuals of African origin, but also by European immigrants, mainly Italian

  10. G6PD deficiency and absence of α-thalassemia increase the risk for cerebral vasculopathy in children with sickle cell anemia.

    Science.gov (United States)

    Joly, Philippe; Garnier, Nathalie; Kebaili, Kamila; Renoux, Céline; Dony, Arthur; Cheikh, Nathalie; Renard, Cécile; Ceraulo, Antony; Cuzzubbo, Daniela; Pondarré, Corinne; Martin, Cyril; Pialoux, Vincent; Francina, Alain; Bertrand, Yves; Connes, Philippe

    2016-04-01

    The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children.

  11. G6PD: The Test

    Science.gov (United States)

    ... RBC Count , Hemoglobin , Autohemolysis Test, Heinz Body Stain, Lactate Dehydrogenase , Haptoglobin All content on Lab Tests Online has ... count and haptoglobin levels , increased reticulocyte count and lactate dehydrogenase levels , presence of bite cells on a blood ...

  12. Analysis of thalassemia and G6PD activity in people of childbearing age%广州市育龄人群地中海贫血和G6PD活性检测结果分析

    Institute of Scientific and Technical Information of China (English)

    刘丽红; 屈艳霞; 余建群; 陈桂兰

    2015-01-01

    目的:了解广州市育龄人群地中海贫血(地贫)和葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症的检出率、地贫患者的G6PD活性、地贫与G6PD活性检测的相互影响。方法抽取21628例受检者的静脉血,采用平均红细胞体积(MCV)、平均红细胞血红蛋白量(MCH)进行地贫初筛,对初筛阳性者进行基因检测;采用酶速率法检测G6PD活性。结果①地贫的检出率为9.94%(2149/21628);② G6PD缺乏症的检出率为7.96%(1721/21628),男、女性别比例为1.96:1;③地贫组(除α-地贫2组)与非地贫组比较,G6PD活性均有不同程度的升高;各种类型地贫组之间G6PD活性增高水平比较,差异有统计学意义(P<0.05);④地贫基因携带合并G6PD缺乏者的MCV、M CH高于地贫基因携带G6PD正常者,差异有统计学意义(P<0.05)。结论本地区是地贫和G6PD缺乏症的高发区;G6PD活性增高的程度不同可作为不同类型地贫的辅助诊断参考指标;G6PD缺乏可影响MCV、MCH筛查地贫的敏感性。%Objective To explore the incidence of thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency, the G6PD activity of patients with thalassemia, and the interaction between thalassemia and G6PD activity. Methods A total of 21 628 people were screened for thalassemia by mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). The people with positive results then underwent thalassemia gene test. The G6PD activities were detected by enzyme kinetic method. Results The incidence of thalassemia was 9.94%(2 149/21 628), and the incidence of G6PD deficiency was 7.96%(1 721/21 628), with male to female ratio of 1.96:1. Compared with non-thalassemia group, the G6PD activities of thalassemia groups all increased significantly, except theα-thalassemia group 2. The increase in G6PD activity showed statistically significant differences between the thal-assemia groups (P<0.05). The people of thalassemia gene complicated with

  13. Impact of G6PD deficiency on plasmodium falciparum malaria%G6PD缺陷症对恶性疟疾感染风险的影响

    Institute of Scientific and Technical Information of China (English)

    陈江涛; 杨辉; 詹小芬; 杨惠钿; 林敏; 刘配芬; 钟德善; 谢东德; Santiago-m Monte-Nguba; Juan Carlos Salas Ehapo; Urbano Monsuy Eyi; 杨立业

    2014-01-01

    Objective To investigate the impact of Glucose-6-phosphate dehydrogenase (G6PD) deficiency on plasmodium falciparum malaria. Methods A cross-sectional study was performed on 2 690 patients in Malabo regional hospital on Bioko Island during rainy season (2012). The plasmodium falciparum was identified by real-time PCR and oil immersion microscopy. G6PD deficiency was identified by a fluorescent spot test (FST) and PCR-DNA sequencing. Logistic regression was conducted to estimate the association between G6PD deficiency and malaria. Results The prevalence of G6PD was 9.22% in the population , all of whose genotype G6PD deficiency was G6PD*A-(c.202 G > A/c.376 A > G). Confounding factors-adjusted OR showed that G6PD deficiency provided significant protection against malaria (P 0.05). Conclusions The results suggest that male hemizygotes could provide protection against malaria. Further studies are required to explore the molecular mechanism in malaria infection.%目的:观察葡萄糖-6-磷酸脱氢酶(G6PD)缺陷症不同表型对恶性疟原虫感染的影响。方法:采用横断面研究的方式,将2012年雨季到马拉博地区医院就诊的2690名比奥克岛当地居民纳入研究。用显微镜镜检、荧光定量 PCR 结合熔解曲线法检测疟原虫。用荧光斑点法及 PCR-DNA 测序鉴定 G6PD 缺陷症。采用 Logistic 回归进行关联性分析。结果:该人群的 G6PD 缺陷症的总发生率为9.22%,基因型均为G6PD*A-(c.202 G>A/c.376 A>G)。G6PD缺陷症体现出强烈的疟疾保护作用(P<0.05);不同性别和表型的 G6PD 缺陷者中,只有男性半合子对疟疾有保护作用(P<0.05),而女性杂合子组与女性纯合子组均无统计学差异(P>0.05)。结论:G6PD 缺陷症的男性半合子表型能够减低恶性疟疾感染的风险,但是其机制尚未明确,有待更深入的研究。

  14. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes.

    Science.gov (United States)

    Rivella, S; Tamanini, F; Bione, S; Mancini, M; Herman, G; Chatterjee, A; Maestrini, E; Toniolo, D

    1995-08-10

    The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5' and 3' moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organization: the transcriptional organization in "domains" described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization.

  15. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes

    Energy Technology Data Exchange (ETDEWEB)

    Rivella, S.; Tamanini, F.; Bione, S.; Mancini, M. [Istituto de Genetica Biochinica ed Evoluzionistica, Pavia (Italy)] [and others

    1995-08-10

    The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5{prime} and 3{prime} moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organizations: the transcriptional organization in {open_quotes}domains{close_quotes} described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization. 17 refs., 4 figs.

  16. Glucosa-6-fosfato deshidrogenasa (G6PD). Respuesta de los hematíes y otras células humanas a la disminución en su actividad

    OpenAIRE

    Javier Fernando Bonilla; Magda Carolina Sánchez; Lilian Chuaire

    2007-01-01

    La glucosa-6-fosfato deshidrogenasa (G6PD) es la primera enzima de la vía pentosa fosfato y la principal fuente intracelular de nicotidamina adenina dinucleótido fosfato reducido (NADPH), compuesto comprometido en diversos procesos fisiológicos, por ejemplo defensa antioxidante (sobre todo células como los eritrocitos), modulación del crecimiento endotelial, eritropoyesis, vascularización y fagocitosis. La deficiencia de G6PD es la enzimopatía ligada al cromosoma X más común en el ser human...

  17. 一种新的G6PD基因突变型的鉴定%IDENTIFICATION OF A NOVEL MUTATION IN HUMAN G6PD GENE

    Institute of Scientific and Technical Information of China (English)

    蔡望伟; 周代锋; 蔡兰洁; 邝宇; 周玉英; FilosaStefania; MartiniGiuseppe

    2003-01-01

    目的:鉴定1例葡萄糖-6-磷酸脱氢酶缺乏症患者的基因突变.方法:用聚合酶链反应、限制性内切酶筛查葡萄糖-6-磷酸酶基因1 388G→A、1 376G→T、1 360C→T、1 024C→T、592C→T、517T→C、493A→G,487G→A、392G→T、95A→G突变,用单链构象多态性筛查葡萄糖-6-磷酸脱氢酶基因的所有外显子,用核苷酸序列测定确定基因突变.结果:该患者未存在1 388G→A、1 376G→T、1 360C→T、1 024C→T、592C→T、517T→C、493A→G、487G→A、392G→T、95A→G突变,但在外显子8发现了一种新的G6PD基因突变--835A→G突变,此突变导致第279位的苏氨酸被丙氨酸取代,将其命名为G6PD-海口,其酶活性约是正常的10%,比835A→T突变型的活性低,后者的酶活性约是正常的40%;分析人G6PD的三维结构模型表明,第279位苏氨酸残基的羟基对于维持G6PD亚基的相互作用具有非常重要的作用.结论:835A→G突变是一种新的G6PD基因突变型,G6PD的第279位苏氨酸残基的羟基是维持G6PD亚基相互作用及酶活性的必需基团.

  18. 珠蛋白生成障碍性贫血患者中葡萄糖-6-磷酸脱氢酶活性的调查%Investigation of G6PD activity in patients with thalassemia

    Institute of Scientific and Technical Information of China (English)

    陈炎添; 苏雪棠

    2012-01-01

    Objective To investigate the activity of glucose 6 phosphate dehydrogenase(G6PD) in patients with different types of thalassemia. Methods G6PD activity,blood cell counts and serum ferritin were detected for preliminary screening,and full auto matic agar gel analyzer was used to confirm the type of α or β thalassemia. G6PD activity of all subjects were statistically analyzed. Results There were statistical difference of G6PD activity between healthy subjects and patients with iron deficiency anemia (IDA) ,IDA combined thalassemia,α thalassemia minor,β thalassemia minor,β thalassemia major,hemoglobin H(HbH) disease and αcombine β thalassemia (P<0. 05). Conclusion The G6PD activity in patients with various types of thalassemia might be increased for different degree. It might be with certain value for auxiliary diagnosis of thalassemia.%目的 研究不同类型珠蛋白生成障碍性贫血(简称地贫)患者中葡萄糖-6-磷酸脱氢酶(G6PD)的活性.方法 采用G6PD活性定量测定,血常规和血清铁蛋白检测对人群进行初筛,同时采用全自动琼脂糖凝胶电泳检测初筛人群的α-地贫以及β-地贫类型,并对其G6PD活性值进行相关统计学分析.结果 健康人群、单纯缺铁性贫血、缺铁性贫血合并地贫、轻型α-地贫、轻型β-地贫、重型β-地贫、血红蛋白H(HbH)病以及α-地贫合并β-地贫各组间G6PD活性差异有统计学意义(P<0.05).结论 各类型地贫患者的G6PD活性有不同程度的升高,对地贫的辅助诊断有一定的价值.

  19. Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in the Han and Li nationalities in Hainan, China and identification of a new mutation in human G6PD gene%海南汉族、黎族人葡萄糖-6-磷酸脱氢酶缺乏症 的基因突变型分析及一种新的G6PD 基因突变型的鉴定

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    目的阐明海南汉族、黎族人群中葡萄糖-6-磷酸脱氢酶缺乏症的分子基础。方法用聚合酶链反应、限制性内切酶消化筛查了1388G→A、1360C→T、1024C→T、592C→T、517T→C、493A→G、487G→A、392G→T和95A→G突变;用单链构象多态性分析筛查其它突变;用核苷酸顺序分析鉴定具有SSCP异常区带样品的突变。结果在59例汉族G6PD缺乏症患者中,发现1388G→A 14例(23.7%)、871G→A 3例(5.1%)、835A→T 1例(1.7%)、517T→C 1例(1.7%)、392G→T 3例(5.1%)和95A→G 4例(6.8%);在32例黎族G6PD缺乏症患者中,发现1388G→A 6例(18.8%)、871G→A 3例(9.4%)和95A→G2例(6.3%);在1例汉族患者中发现了一种新的G6PD基因突变——835A→G突变,此突变导致第279位的苏氨酸被丙氨酸取代,将此突变型命名为G6PD-海口,其酶活性约是正常的10%,比835A→T突变的活性低,后者的酶活性约是正常的40%。分析人G6PD的三维结构模型表明,第279位苏氨酸残基的羟基是维持G6PD亚基相互作用的基团。结论海南汉族、黎族人群中具有共同的常见G6PD基因突变型;与中国其它地区人群的G6PD基因突变谱比较,结果表明某些G6PD基因突变广泛分布于中国南方不同地区人群中;G6PD第279位苏氨酸残基的羟基可能是维持G6PD亚基相互作用及酶活性的必需基团。%Objective  To elucidate the molecular basis of G6PD deficiency in the Han and Li nationalities in Hainan, China. Methods  Polymerase chain reaction and restriction enzyme digestion were used to screen the mutations 1388G→A, 1360C→T, 1024C→T, 592C→T,517T→C, 493A→G,487G→A,392G→T and 95A→G. Single strand conformation polymorphism analysis was used to screen the other mutations followed by DNA sequencing to characterize the mutations of the samples with abnormal SSCP bands. Results  Of the fifty-nine Han cases with G6PD deficiency, fourteen with 1388G→A(23

  20. Glucosa-6-fosfato deshidrogenasa (G6PD. Respuesta de los hematíes y otras células humanas a la disminución en su actividad

    Directory of Open Access Journals (Sweden)

    Javier Fernando Bonilla

    2007-03-01

    Full Text Available La glucosa-6-fosfato deshidrogenasa (G6PD es la primera enzima de la vía pentosa fosfato y la principal fuente intracelular de nicotidamina adenina dinucleótido fosfato reducido (NADPH, compuesto comprometido en diversos procesos fisiológicos, por ejemplo defensa antioxidante (sobre todo células como los eritrocitos, modulación del crecimiento endotelial, eritropoyesis, vascularización y fagocitosis. La deficiencia de G6PD es la enzimopatía ligada al cromosoma X más común en el ser humano. Si bien se puede presentar en cualquier tipo de célula, su carencia absoluta es incompatible con la vida. Según la OMS, en el mundo hay más de 400 millones de personas afectadas por la deficiencia de la enzima, y para Colombia calculan una prevalencia de la deficiencia severa entre 3% y 7%, pero no se conocen los datos relativos a las alteraciones leves y moderadas, que también tienen efectos clínicos. El presente artículo revisa los aspectos biomoleculares más importantes de la enzima, su clasificación de acuerdo con la actividad y la movilidad electroforética, y también se mencionan algunos aspectos clínicos relacionados con la alteración de su actividad.

  1. Clinical analysis of 5 cases of sickle cell disease combinded G6PD deficiency.%镰状细胞病合并G6PD缺陷症五例临床分析

    Institute of Scientific and Technical Information of China (English)

    谢庆芳; 李菊香; 苏运钦; 尹更生; 谭润平

    2010-01-01

    目的 总结5例血红蛋白S病(HbS)各类实验数据,为临床提供实验诊断,预防新生儿的严重并发症.方法 血常规检测,全自动血红蛋白电泳,G6PD/6PGD直接比值法,G6PD/6PGD全自动生化仪日立7600检测G6PD缺陷症.结果 检测5例HbS患者,发现合并a地贫1例,4例合并G6PD缺陷症.结论 Hb电泳区带定量是诊断HbS的重要方法.镰变试验是鉴别HbS与HbD的确诊试验.G6PD缺陷症在非洲裔HbS患者中有较高的发生率,如果同时合并2种遗传病会加重贫血症状.

  2. 遗传性球形红细胞增多症合并G6PD缺乏1例报告%Hereditary spherocytosis accompanied with G6PD deifciency:a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    马诗玥; 林发全

    2016-01-01

    Objective To discuss the clinical features, pathogenesis and diagnostic experience of hereditary spherocytosis (HS) accompanied with glucose-6-phosphate dehydrgenase deficiency (G6PD) deficiency.Methods Clinical features and diagnose of a 5-year-old case with HS accompanied with G6PD deifciency were analyzed, and realated literatures reviewed. Results The case was a 5-year-old boy referred to a hospital because of pallor and jaundice. Laboratory test results were as follows: red blood cell count 2.65×1012/ L, hemoglobin 70.50 g/L, mean corpuscular volume 78.61 fl, and mean sphered corpuscular volume 66.26 lf, reticulocyte ratio 18%; G6PD activity was 1.38 NBT. The peripheral red blood cells were of different sizes and mature, and spherocytes were observed. SDS-polyacrylamide gel electrophoresis and western blot shows the band 3 was partially deletion. Molecular analysis revealed the band 3 deifciency was caused by two mutations: one was a missensemutation c.113A> C, and the other was a intron mutation c.349+27C> T. A diagnosis of HS accompanied with G6PD deifciency was therefore arrived.Conclusions HS accompanied with G6PD deifciency is a relatively uncommon phenomenon and might lead to misdiagnosis. Blood smear staining, thalassemia screening, mean sphered corpuscular volume and other laboratory detections could improve the accuracy of diagnosis.%目的:探讨遗传性球形红细胞增多症(HS)合并葡萄糖-6-磷酸脱氢酶(G 6 PD)缺乏症的临床表现、发病机制和诊断经验。方法回顾分析1例5岁HS合并G 6 PD缺乏症患儿的临床表现、实验室检查,并复习国内外相关文献。结果患儿,男,5岁。因面色苍白伴黄疸,疑似地中海贫血就诊。红细胞计数2.65×1012/L,血红蛋白70.50 g/L,平均红细胞体积78.61 lf,平均球形红细胞体积66.26 lf,网织红细胞18%;镜检红细胞大小不等,以小细胞为主,球形红细胞约占15%;G6PD活性1.38 NBT;SDS-PAGE

  3. 宝鸡地区192469例新生儿G6PD筛查结果分析%Analysis of 192 469 Cases of Neonatal G6PD Screening Results

    Institute of Scientific and Technical Information of China (English)

    张娟玲; 唐凯; 刘郁明; 成艳; 屈萍; 王文娟; 杜小云; 权秋宁

    2016-01-01

    目的 探讨本地区新生儿葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症的发病情况以采取措施预防因G6PD缺乏而引起的一系列疾病的发生,保护新生儿的健康成长.方法 采取新生儿出生后72h滤纸干血样应用时间分辨(DELFIA)荧光法检测G6PD含量.结果 192469例新生儿中G6PD缺乏症筛查试验阳性者48例,全市新生儿G6PD缺乏症发病率为2.49/万.其中陕西省籍贯为18例(检出率37.5%),外省籍贯为30例(检出率为62.5%),x2=6.00,0.01<P<0.05.其中患儿母亲为广西籍贯者15例(占50%);贵州籍贯3例(占10%);广东籍贯6例(占20%);甘肃、河南、浙江、福建、海南、四川籍贯各1例(各占3.33%).结论 本地区新生儿G6PD缺乏症发病率低于南方地区,但G6PD缺乏症高发区人口流入可增加本地区的发生率,因此应对G6PD高发区流入人群给予充分关注,对患儿进行早期干预并对家长进行健康教育,避免因核黄疸而引起患儿死亡和智能发育障碍.%Objective:To prevent the occurrence of a series of diseases induced by G6PD deficiency and to guarantee healthy growth of newborn,the incidence of local neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency was discussed in this paper.Methods:Time-resolved (DELFIA) fluorescence was applied to detect the concentration of G6PD in filter paper dried blood samples of 72h after birth.Results:48 cases of G6PD deficiency positive infants were detected during 192 469 cases of newborn,and the morbidity of G6PD deficiency in the whole city was 2.49/10000.There were 18 cases in the province of Shaanxi (detectable rate was 37.5%),and 30 cases were in other provinces (detectable rate was 62.5%),x2=6.00,0.01<P<0.05.15 cases of the infants'mothers came from Guangxi province (accounted for 50%),3 cases from Guizhou province (accounted for 10%),6 cases from Guangdong Province (accounted for 20%),and 1 case respectively from Gansu,Henan,Zhejiang,Fujian,Hainan and

  4. 赤道几内亚比奥科岛G6PD缺乏症分子流行病学研究%Molecular epidemiological investigation of the G6PD deficiency on Bioko Island, Equatorial Guinea

    Institute of Scientific and Technical Information of China (English)

    詹小芬; 陈江涛; 谢东德; 杨辉; 杨惠钿; 杨立业; 陆志为; Santiago-m Monte-Nguba; Juan Carlos Salas Ehapo

    2014-01-01

    目的 探讨非州西部赤道几内亚比奥科岛(Bioko Island)人群的葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症的发生率及基因型. 方法 在2012年1月至5月期间,用荧光斑点法对2 187名比奥科岛当地居民进行G6PD缺乏症筛查.采用高分辨熔解曲线(High-resolution melting,HRM)分析G6PD缺乏的标本的c.202 G>A与c.376 A>G.对HRM筛选不出突变的G6PD酶学缺乏的样本,针对非洲的其他突变类型:c.542 A>T(rs5030872)、c.680 G>A(rs137852328)、c.968 T>C(rs76723693)进行PCR-DNA测序. 结果 赤道几内亚比奥科岛人群的G6PD缺乏症总发生率为8.64% (189/2 187),其中男性84例(9.04%,84/929),女性105例(8.34%,105/1 258),男女检出率比为1.08:1.在189例G6PD缺乏标本中共检出两种基因类型,其中包括G6PD A变异体(c.376 A>G/c.202 G>A)186例(98.41%,186/189G6PD Betica(c.376 A>G/c.968T> C)3例(1.59%3/189). 结论 赤道几内亚比奥科岛是G6PD缺乏症高发区,基因型比较单一.HRM技术可用于非洲地区G6PD缺乏症的临床诊断和流行病学研究.

  5. Genetic diversity of hemoglobinopathies, G6PD deficiency, and ABO and Rhesus blood groups in two isolates of a primitive Kharia Tribe in Sundargarh District of Northwestern Orissa, India.

    Science.gov (United States)

    Balgir, R S

    2010-09-01

    Tribal communities constitute about 8.2% of the total population of India. Their health needs are even larger than elsewhere in India; this study investigates the genetic diversity in relation to hemoglobinopathies, G6PD deficiency and, ABO and Rhesus (D) blood groups in two sects, i.e. Dudh (converted Christian) and Dhelki (Hinduised) Kharia, a primitive tribe in Sundargarh district of Orissa in Central-Eastern India. A randomized screening of 767 Kharia tribals (377 males and 390 females) belonging to all age groups and both sexes was done. Laboratory analysis was carried out following the standard methodology and techniques. Contrasting differences were observed in the frequency of hematological genetic disorders such as β-thalassemia, sickle cell, hemoglobin E, G6PD deficiency, ABO and Rhesus (D) blood groups between the two subgroups. Dudh Kharia had no hemoglobin variant allele other than the high prevalence of β-thalassemia trait (8.1%), whereas, their counterpart Dhelki Kharia had the high prevalence of sickle cell allele (12.4%), hemoglobin E allele (3.2%), and β-thalassemia allele (4.0%). Frequency distribution of hemoglobin variants between Dudh and Dhelki Kharia tribe was statistically highly significant (p blood group was 1.1% in Dudh Kharia and absent in Dhelki Kharia (p < 0.05). This study showed genetic isolation of the two sects of Kharia tribe. Antimalarial drugs administration needs to be done with caution. Hematological disorders pose a major health challenge having multifaceted implications in public health genetics.

  6. 黄酮类化合物对葡萄糖-6-磷酸脱氢酶缺乏者红细胞的体外氧化作用%The oxidative effects of flavonoids on G6PD-deficient erythrocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    张婧; 张志豪; 黎曙霞

    2011-01-01

    目的:探讨黄酮类化合物对葡萄糖-6-磷酸脱氢酶(G6PD)缺乏者红细胞氧化还原状态的影响.方法:将低、中、高浓度的槲皮素、黄芩素、芹菜素、漆黄素、木犀草素、柚皮素、桑黄素、山奈酚、葛根素和芦丁分别与G6PD缺乏者及正常者红细胞在40%红细胞悬液和全血中进行体外孵育,测定红细胞还原性谷胱甘肽(GSH)和高铁血红蛋白(MetHb)的水平.结果:槲皮素、黄芩素、芹菜素、漆黄素、木犀草素、柚皮素、桑黄素、山奈酚具有较强的氧化作用,能明显降低G6PD缺乏者红细胞GSH水平,升高MetHb水平.葛根素仅降低G6PD缺乏者红细胞GSH水平,具有较弱的氧化作用.芦丁对G6PD缺乏者红细胞GSH和MetHb均无影响.较高浓度的槲皮素、芹菜素、桑黄素亦能使G6PD正常者MetHb水平升高.黄酮类化合物的氧化作用呈一定浓度依赖性,在中、高浓度时表现明显.结论:部分黄酮类化合物对G6PD缺乏者红细胞具有氧化作用,建议G6PD缺乏者慎用富含氧化性黄酮类化合物的中草药及其制剂.%OBJECTIVE To investigate the effects of flavonoids on the oxidative and reductive status of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes. METHODS The G6PD-deficient and normal erythrocytes of 40% erythrocyte suspension and whole blood were respectively incubated with quercetin, baicalein, apigenin, fisetin, luteolin, naringenin, morin, kaempferol,puerarin and rutin at low, medium and high concentrations in vitro. The resulting levels of reduced glutathione (GSH) and methemoglobin (MetHb) of erythrocytes in each group were determined. RESULTS Quercetin,baicalein,apigenin, fisetin,luteolin,naringenin,morin,kaempferol with strong oxidative effects significantly reduced GSH and increased MetHb levels in G6PD-deficient erythrocytes. Puerarin which possessed weak oxidative effect just caused GSH reduced in G6PD-deficient erythrocytes. Rutin had no effects on both

  7. 广西地区不同地中海贫血类型G6PD酶活性水平初步研究%Study of the levels of G6PD activity in different types of thalassemia in Guangxi

    Institute of Scientific and Technical Information of China (English)

    赵林; 温乃健; 宁乐平; 梁亮; 韦金花; 李友琼

    2015-01-01

    Objective To analyse the levels of G6PD activity in different types of thalassemia in Guangxi and to study their association with thalassemia.Me thods One hundred and thirteen negative thalassemia samples and 248 different types of thalassemia samples were analyzed by gene analysis and were detected for G6PD activity.Re-sults The levels of G6PD activity was (6.76 ±2.28)U/gHb in the negative thalassemia group, (9.00 ±3.67 )U/gHb inαthalassemia group, (10.98 ±6.25) U/gHb in βthalassemia group, and (9.09 ±2.96) U/gHb in αβcomplex thalassemia group, with significantly differences compared with the negative thalassemia group ( P <0.05 ) .The G6PD activity levels ofαthalassemia in silent, trait and Hb H groups were (6.67 ±1.65)U/gHb,(8.89 ±2.12)U/gHb, (12.7 ±5.44)U/gHb respectively;of βthalassemia in trait and intermedia groups were (9.68 ±3.71)U/gHb and (18.43 ±10.71)U/gHb.There were significant differences in the levels of G6PD between the different types of αthalassemia andβthalassemia inαthalassemia and βthalassemia groups(P<0.05).Conclusion Different levels of G6PD activity go with different types of thalassemia, the more severe anemia the higher G6PD activity.%目的了解广西地区不同地中海贫血类型患者的葡萄糖-6-磷酸脱氢酶(G6PD)酶活性水平,探讨其与地中海贫血的关联性。方法对经过地中海贫血基因分析确诊阴性的113名健康人群和248例不同地中海贫血类型的患者进行G6PD 酶活性检测,并对结果进行统计学分析。结果健康人群组的G6PD 酶活性水平为(6.76±2.28)U/gHb,α地中海贫血为(9.00±3.67)U/gHb,β地中海贫血为(10.98±6.25)U/gHb,αβ复合型地中海贫血为(9.09±2.96)U/gHb,与健康人群组比较差异均有统计学意义(P <0.05)。α地中海贫血中静止型、轻型和中间型的G6PD 酶活性水平分别为(6.67±1.65)、(8.89±2.12)和(12.7±5.44

  8. The present situation of thalassemia and G - 6PD deficiency in pregnant women in Shenzhen Baoan area.%深圳宝安地区孕妇地中海贫血和G-6PD缺乏现状调查研究分析

    Institute of Scientific and Technical Information of China (English)

    刘爱胜; 陈荣贵; 文艳

    2011-01-01

    目的 调查研究深圳宝安地区孕妇地中海贫血和葡萄糖-6-磷酸脱氢酶(G-6PD)缺乏发生率现状,探讨产前筛查地中海贫血和G-6PD的临床价值.方法 应用地中海贫血一管筛查法和G-6PD比值法检测孕14~20周孕妇5 976例,筛查其地中海贫血及G-6PD缺乏症发生率.同时,对筛查地中海贫血阳性者进行血红蛋白电泳分型.结果在5 976例受检者孕妇中,地中海贫血者为372例,G-6PD缺乏者为286例,检出率分别为6.2%(372/5976)和4.8%(286/5976).检出α地中海贫血163例,占43.8%(163/372),β-地中海贫血189例,占50.8%(189/372),其它类型异常血红蛋白5.4%(20/372).结论 在地中海贫血高发区进行产前地中海贫血和G-6PD缺乏的筛查,是避免重型地中海贫血患儿的出生及新生儿溶血黄疸的有效措施.%Objective To investigate the incidence of thalassemia and G - 6PD deficiency in pregnant woman in Baoan, Shenzhen, and discuss the clinical value of pre - natal screening of thalassemia and G - 6PD. Methods Thalassemia and G - 6PD deficiency were screened with the examinations of osmotic fragility and relative value of G - 6PD respectively in 5976 14 ~ 20 weeks pregnant women. Hemoglobin electrophoresis was further performed for pregnant women with positive thalassemia screening results. Results Of 5976 pregnant women, thalassemia and G - 6PD deficiency were found in 372 ( 6.2% ) and 286 ( 4.8% ) respectively. The classification of the 372 thalassemia patients included α - thalassemia in 163 ( 43.8%, 163/372 ), β - thalassemfia in 189 ( 50.8%, 189/372 ) and other type abnormal hemoglobin in 20 ( 5.4%, 20/372 ). Conclusion Pre - natal screening of thalassemia and G - 6PD deficiency is effective in the prevention of thalassemia and hemolytic jaundice of the newborn.

  9. 云南10个民族7岁以下儿童血红蛋白病与G6PD缺乏症的调查%Investigation on hemoglobinopathy and G6PD deficiency among the Children under 7 years of ten ethnic groups in Yunnan

    Institute of Scientific and Technical Information of China (English)

    姚莉琴; 王兴田; 邹团标; 陈谦; 杨发斌; 忽丽莎; 范丽梅; 全星; 赵钟鸣; 刘锦桃

    2011-01-01

    目的:了解云南三边境州10个特有少数民族的7岁以下儿童血红蛋白病和G6PD缺乏症的现状.方法:血红蛋白病检测:对调查者应用日本SysmexKX - 21N和迈瑞- 2000血细胞分析仪进行血细胞分析,醋酸纤维薄膜电泳检测血红蛋白,DNA序列分析及ARMS基因检测;G6PD缺乏症检测采用改良葡萄糖6-磷酸脱氢酶(G6PD)比值法.结果:地贫检出率以德宏州最高(46.2%),怒江州最低(30.6%),版纳州居中.β-地贫以阿昌族居首位40.6% (39/96),独龙族最低为2.5%(5/204).α--地贫以版纳傣族最高为22.1%(266/1204),其次为独龙族19.1% (39/204).G6PD缺乏症检出率德宏州为6.7%(146/2190),版纳州为2.2% (60/2780),怒江州为1.0% (14/1407).G6PD缺乏症以德昂族最高为8.6% (30/349),其次为阿昌族7.3% (19/261).异常血红蛋白检出率为2.4%.结论:血红蛋白病和G6PD缺乏症在云南省三边境州10个特有少数民族7岁以下儿童属高发,血红蛋白病和G6PD缺乏症的人群地理分布与历史上疟疾流行的地理分布存在着一定的相关性.%Objective: To understand the current situations of hemoglobinopathy and G6PD deficiency among the children under 7 years of ten ethnic groups in border of Yunnan. Methods: Detection of hemoglobin; the children received blood cell analysis by Japanese SysmexKX - 21N blood cell analyzer and Mindray - 2000 blood cell analyzer, cellulose acetate membrane electrophoresis was used to detect hemoglobin, DNA sequence analysis and ARMS gene detection were conducted. Detection of G6PD deficiency: modified G6PD ratio method was used. Results: The incidence of thalassaemia in Dehong prefecture was the highest (46. 2% ) , the incidence of thalassaemia in Nujiang prefecture was the lowest ( 30. 6% ) , the incidence of thalassaemia in Banna prefecture was moderate. The incidence of β - thalassaemia in children of Achang nationality was the highest (40. 6% , 39/96) , the incidence of p

  10. 新生儿脐血地贫筛查和葡萄糖-6-磷酸脱氢酶缺乏的分析%Prenatal screening of thalassemia in 7210 samples of neonatal cord blood and G6PD deficiency

    Institute of Scientific and Technical Information of China (English)

    余小燕; 余相; 张丽科

    2010-01-01

    目的 探讨经过规律产检和遗传咨询新生儿血红蛋白病和红细胞酶疾病的发病率的控制情况.方法 应用血红蛋白电泳和葡萄糖-6-磷酸脱氢酶(G6PD)比值法检查7210例新生儿的脐血血红蛋白电泳区带和G-6-PD结果.结果 筛查7210例新生儿脐血中,检出G6PD缺乏患儿150例,静止型α-地贫85例,标准型α-地贫205例,检出率各为4.48%、2.54%、6.13%.09年检出G6PD缺乏患儿166例,静止型α-地贫95例,标准型α-地贫220例,检出率各为4.30%、2.46%、5.69%.同比下降分别为0.18%、0.08%、0.44%.结论 经过正规的产检和遗传咨询后确认为低风险的新生儿出生后发病的概率比预测的概率减低,且产检和遗传咨询对预防重度地贫患儿的出生有重大的作用.%Objective To explore the incidence of newborn hemoglobinopathy and erythrocyte enzyme disorders after regular prenatal visits and genetic consulting. Methods The band on hemoglobin electrophoresis and the G6PD level were detected in 7210 samples of umbilical cord blood by hemoglobin electrophoresis and G6PD ratio method. Results Of 7210 samples,the detection rate of G6PD deficiency was 4.38%. The detected rates of α -thalassemia with a/a mutation and standard α-thalassemia were 2.50%and 5.89%. The incidence of the three disorders in 2009 was decreased by 0.18%,0.08%,and 0.44%,as compared with 2008. Conclusions The probability of the incidence of the disorders reduces in the confirmed low-risk neonates after regular prenatal visits and consulting,as compared with the predictive probability. Prenatal visits and genetic consulting play an important role in preventing the birth rate of neonates with severe thalassemia.

  11. A 11-Steps Total Synthesis of Magellanine through a Gold(I)-Catalyzed Dehydro Diels-Alder Reaction.

    Science.gov (United States)

    McGee, Philippe; Bétournay, Geneviève; Barabé, Francis; Barriault, Louis

    2017-01-12

    We have developed an innovative strategy for the formation of angular carbocycles via a gold(I)-catalyzed dehydro Diels-Alder reaction. This transformation provides rapid access to a variety of complex angular cores in excellent diastereoselectivities and high yields. The usefulness of this Au(I) -catalyzed cycloaddition was further demonstrated by accomplishing a 11-steps total synthesis of (±)-magellanine.

  12. Non-oxidative dehydro-oligomerization of methane to higher molecular weight hydrocarbons at low temperatures

    Institute of Scientific and Technical Information of China (English)

    王林胜; 徐奕德; 陶龙骧

    1997-01-01

    The non-oxidative dehydro-oligomerization of methane to higher molecular weight hydrocarbons such as aroma tics and C2 hydrocarbons in a low temperature range of 773-973 K with Mo/HZSM-5,Mo-Zr/HZSM-5 and Mo-W/HZSM-5 catalysts is studied.The means for enhancing the activity and stability of the Mo-containing catalysts under the reaction conditions is reported.Quite a stable methane conversion rate of over 10% with a high selectivity to the higher hydrocarbons has been obtained at a temperature of 973 K.Pure methane conversions of about 5.2% and 2.0% have been obtained at 923 and 873 K,respectively.In addition,accompanied by the C2-C3 mixture,tht- methane reaction can be initiated even at a lower temperature and the conversion rate of methane is enhanced by the presence of tne initiator of C2-C3 hydrocarbons.Compared with methane oxidative coupling to ethylene,the novel way for methane transformation is significant and reasonable for its lower reaction temperatures and high selectivity to the desired prod

  13. Evidence for the formation of a quinone methide during the oxidation of the insect cuticular sclerotizing precursor 1,2-dehydro-N-acetyldopamine.

    Science.gov (United States)

    Sugumaran, M; Semensi, V; Kalyanaraman, B; Bruce, J M; Land, E J

    1992-05-25

    1,2-Dehydro-N-acetyldopamine (dehydro-NADA) is an important catecholamine derivative involved in the cross-linking of insect cuticular components during sclerotization. Since sclerotization is a vital process for the survival of insects, and is closely related to melanogenesis, it is of interest to unravel the chemical mechanisms participating in this process. The present paper reports on the mechanism by which dehydro-NADA is oxidatively activated to form reactive intermediate(s) as revealed by pulse radiolysis, electron spin resonance spectroscopy, high performance liquid chromatography, and ultraviolet-visible spectroscopic analysis. Pulse radiolytic one-electron oxidation of dehydro-NADA by N3. (k = 5.3 x 10(9) M-1 s-1) or Br2.- (k = 7.5 x 10(8) M-1 s-1) at pH6 resulted in the rapid generation of the corresponding semiquinone radical, lambda max 400 nm, epsilon = 20,700 M-1 cm-1. This semiquinone decayed to form a second transient intermediate, lambda max 485 nm, epsilon = 8000 M-1 cm-1, via a second order disproportionation process, k = 6.2 x 10(8) M-1 s-1. At pH 6 in the presence of azide, the first order decay of this second intermediate occurred over milliseconds; the rate decreases at higher pH. At pH 6 in the presence of bromide, the intermediate decayed much more slowly over seconds, k = 0.15 s-1. Under such conditions, the dependence of the first order decay constant upon parent dehydro-NADA concentration led to a second order rate constant of 8.5 x 10(2) M-1 s-1 for reaction of the intermediate with the parent, probably to form benzodioxan "dimers." (The term dimer is used for convenience; the products are strictly bisdehydrodimers of dehydro-NADA (see "Discussion" and Fig. 11)) Rate constants of 5.9 x 10(5), 4.5 x 10(5), 2.8 x 10(4) and 3.5 x 10(4) M-1 s-1 were also obtained for decay of the second intermediate in the presence of cysteine, cysteamine, o-phenylenediamine, and p-aminophenol, respectively. By comparison with the UV-visible spectroscopic

  14. MOLECULAR BASIS OF G6PD DEFICIENCY: CURRENT STATUS AND ITS PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    M. R. Noori-Daloii

    2008-06-01

    Full Text Available Glucose-6-phosphate dehydrogenase is an essential enzyme to cell growth. Its deficiency of enzyme plays an important role in senescence and death signaling. Also, it is actually the most common clinically important enzyme defect, not only in hematology, but also among all human known diseases. Clinical consequences of enzyme deficiency are: neonatal hyperbilirubinemia, acute hemolytic anemia, and chronic hemolytic anemia. The enzyme gene spans 18 kb on the X chromosome (xq28 and contains 13 exons. Its promoter is embedded in a CpG island that is conserved from mice to humans. The development of a number of PCR-based methods for the detection of known mutations in Glucose-6-phosphate dehydrogenase has made it possible to detect enzyme deficiency and identify the specific mutation responsible with relative ease. We will discuss the mentioned clinical manifestations of glucose-6-phosphate dehydrogenase deficiency, Genetics, biochemistry and pathophysiology of the enzyme in details using newer published data and present most of the studies in Iranian population.

  15. Luminescent Nitro Derivatives of 5,11-Dehydro-5H, 11H-benzotriazolo(2,1- alpha)benzotriazole

    Science.gov (United States)

    1992-08-07

    2,1-a]benzotriazole lib were obtained from 3,4- diaminotoluene 12 and 4,5-dimethyl-l,2-phenylenediamine 13 via the inter- 5 mediate dimethyl and...the mixture was poured into ice- water . A precipitate was isolated and recrystallized from dimethylformamide to give 2,4,8-tn- nitro-5,11-dehydro-5H...stored for 4 h. An orange-red solid wa! isolated, washed with water , and dried. Purification by column chromatography (silica gel, dichloro- methane

  16. Oxidative Lung Injury in Virus-Induced Wheezing

    Science.gov (United States)

    2015-07-01

    units. All experiments were performed at least two to three times. Determination of lactate dehydrogenase activity. Lactate dehydro- genase (LDH...Effect of EUK treatment on RSV-induced lactate dehydrogenase (LDH) release. A549 cells were infected with RSV in the absence or presence of different M...are expressed in arbitrary units. Determination of lactate dehydrogenase activity. Lactate dehydro- genase (LDH) activity in the medium, an index of

  17. Development and validation of a high-performance liquid chromatography method using diode array detection for the simultaneous quantification of aripiprazole and dehydro-aripiprazole in human plasma.

    Science.gov (United States)

    Lancelin, Frédérique; Djebrani, Kayssa; Tabaouti, Khalid; Kraoul, Linda; Brovedani, Sophie; Paubel, Pascal; Piketty, Marie-Liesse

    2008-05-01

    A high-performance liquid chromatography method with diode array detection (HPLC-DAD) was developed for quantification of aripiprazole and dehydro-aripiprazole, in human plasma. After a simple liquid-liquid extraction, chromatographic separation was carried out on a C18 reversed-phase column, using an ammonium buffer-acetonitrile mobile phase (40:60, v/v). The total run time was only 7 min at a flow-rate of 1.0 ml/min. The precision values were less than 12% and the accuracy values were ranging from 98 to 113% and the lower limit of quantification was 2 ng/ml for both compounds. Calibration curves were linear over a range of 2-1000 ng/ml. The mean trough plasma concentrations in patients treated with aripiprazole were 157 and 29 ng/ml for aripiprazole and dehydro-aripiprazole, respectively.

  18. Severe G6PD Deficiency Due to a New Missense Mutation in an Infant of Northern European Descent

    DEFF Research Database (Denmark)

    Warny, Marie; Lausen, Birgitte; Birgens, Henrik

    2015-01-01

    We report a term male infant born to parents of Danish descent, who on the second day of life developed jaundice peaking at 67 hours and decreasing on applied double-sided phototherapy. In the weeks following, the infant showed signs of ongoing hemolysis. Laboratory tests showed very low glucose-...

  19. Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    Nejal M. Bhatt; Vijay D. Chavada; Daxesh P. Patel; Primal Sharma; Mallika Sanyal; Pranav S. Shrivastav

    2015-01-01

    A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs). Plasma samples were prepared using solid phase extraction 18 (50 mm ? 2.1 mm, 1.7 mm) column. The method was established over a concentration range of 0.5–1000 ng/mL for cilostazol and 0.5–mL for 3,4-dehydro cilostazol. Intra-and inter-batch precision (%CV) and accuracy for the analytes were found within 0.93–1.88 and 98.8–101.7% for cilostazol and 0.91–2.79 and 98.0–102.7% for the metabolite respectively. The assay recovery was within 95–97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects.

  20. Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC−MS/MS

    Directory of Open Access Journals (Sweden)

    Nejal M. Bhatt

    2015-02-01

    Full Text Available A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC−MS/MS method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs. Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm column. The method was established over a concentration range of 0.5–1000 ng/mL for cilostazol and 0.5–500 ng/mL for 3,4-dehydro cilostazol. Intra- and inter-batch precision (% CV and accuracy for the analytes were found within 0.93–1.88 and 98.8–101.7% for cilostazol and 0.91–2.79 and 98.0–102.7% for the metabolite respectively. The assay recovery was within 95–97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects.

  1. Synthesis and absolute configuration of a new 3,4-dihydro-beta-carboline-type alkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Uncaria tomentosa).

    Science.gov (United States)

    Kitajima, Mariko; Yokoya, Masashi; Takayama, Hiromitsu; Aimi, Norio

    2002-10-01

    The structure including the absolute configuration of a new glucoalkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa), was confirmed by synthesis starting from secologanin and L-tryptophan.

  2. Methane dehydro-aromatization over Mo/HZSM-5 catalysts in the absence of oxygen: Effect of steam-treatment on catalyst stability

    Institute of Scientific and Technical Information of China (English)

    Tingting Zhao; Hongxia Wang

    2011-01-01

    The effect of steam-treatment to HZSM-5 zeolite and Mo/HZSM-5 with a steaming time range of 0.5-1 h on the catalytic performance of methane dehydro-aromatization (MDA) over Mo/HZSM-5 catalyst prepared with impregnation has been studied in detail in combination with the characterization of 1H MAS NMR technique.Both the deactivation rate constant (kd) and the Br(o)nsted acid sites per unit cell were calculated to quantitatively evaluate the stability of Mo/HZSM-5 catalysts treated with steam at 813 K before and after impregnation of molybdenum species,and the corresponding variation of their Br(o)nsted acid sites.The results reveal that a V-shape relationship between kd and the number of B 1 acid sites per unit cell is presented on Mo/HZSM-5 catalyst under the tested steam-treatment and reaction conditions.

  3. Inhibition of LPS binding to MD-2 co-receptor for suppressing TLR4-mediated expression of inflammatory cytokine by 1-dehydro-10-gingerdione from dietary ginger

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sun Hong; Kyeong, Min Sik; Hwang, Yuri [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Ryu, Shi Yong [Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Han, Sang-Bae [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Youngsoo, E-mail: youngsoo@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer 1-Dehydro-10-gingerdione (1D10G) from ginger inhibits LPS binding to MD-2. Black-Right-Pointing-Pointer 1D10G suppresses MyD88- or TRIF-dependent signaling in LPS-activated macrophages. Black-Right-Pointing-Pointer 1D10G down-regulates the expression of NF-{kappa}B-, AP1- or IRF3-target genes. Black-Right-Pointing-Pointer MD-2 is a molecular target in the anti-inflammatory action of 1D10G. -- Abstract: Myeloid differentiation protein 2 (MD-2) is a co-receptor of toll-like receptor 4 (TLR4) for innate immunity. Here, we delineated a new mechanism of 1-dehydro-10-gingerdione (1D10G), one of pungent isolates from ginger (Zingiber officinale), in the suppression of lipopolysaccharide (LPS)-induced gene expression of inflammatory cytokines. 1D10G inhibited LPS binding to MD-2 with higher affinity than gingerol and shogaol from dietary ginger. Moreover, 1D10G down-regulated TLR4-mediated expression of nuclear factor-{kappa}B (NF-{kappa}B) or activating protein 1 (AP1)-target genes such as tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin-1{beta}, as well as those of interferon (IFN) regulatory factor 3 (IRF3)-target IFN-{beta} gene and IFN-{gamma} inducible protein 10 (IP-10) in LPS-activated macrophages. Taken together, MD-2 is a molecular target in the anti-inflammatory action of 1D10G.

  4. 4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage

    Science.gov (United States)

    Zhong, Guannan; Zhao, Qunfei; Zhang, Qinglin; Liu, Wen

    2017-07-01

    γ-Glutamyltranspeptidases (γ-GTs), ubiquitous in glutathione metabolism for γ-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)-hydrolase fold proteins that share an autoproteolytic process for self-activation. γ-GT homologues are widely present in Gram-positive actinobacteria where their Ntn-hydrolase activities, however, are not involved in glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L-(dehydro)proline (ALDP) residues, the non-proteinogenic α-amino acids that serve as vital components of many bioactive metabolites found in actinobacteria, involves unprecedented Ntn-hydrolase activity of γ-GT homologue for C-C bond cleavage. The related enzymes share a key Thr residue, which acts as an internal nucleophile for protein hydrolysis and then as a newly released N-terminal nucleophile for carboxylate side-chain processing likely through the generation of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights into the biosynthesis of various ALDP residues/associated natural products, highlight the versatile functions of Ntn-hydrolase fold proteins, and particularly generate interest in thus far less-appreciated γ-GT homologues in actinobacteria.

  5. Self-Assembled Dehydro[24]annulene Monolayers at the Liquid/Solid Interface: Toward On-Surface Synthesis of Tubular π-Conjugated Nanowires.

    Science.gov (United States)

    Suzuki, Mitsuharu; Guo, Zhaoqi; Tahara, Kazukuni; Kotyk, Juliet F Khosrowabadi; Nguyen, Huan; Gotoda, Jun; Iritani, Kohei; Rubin, Yves; Tobe, Yoshito

    2016-06-07

    We have studied the self-assembly behavior of dehydro[24]annulene (D24A) derivatives 1, 2a-2d, and 3a-3c at the liquid/solid interface using scanning tunneling microscopy (STM). Both the relative placement and the nature of the four D24A substituents strongly influence the self-assembly pattern. Overall, the eight D24A derivatives examined in this study display seven types of 2D packing patterns. The D24A derivatives 1, 2a, and 3a have either two or four stearate groups and adopt face-on configurations of their macrocyclic cores with respect to the highly oriented pyrolytic graphite (HOPG) surface. Their 2D packing pattern is determined by the interchain spacings and number of stearate substituents. The D24A derivatives 2b-2d and 3b-3c bear hydrogen-bonding carbamate groups to further strengthen intermolecular interactions. Face-on patterns were also observed for most of these compounds, while an unstable edge-on self-assembly was observed in the case of 2b at room temperature. Stable edge-on self-assemblies of D24A derivatives were sought for this work as an important stepping stone to achieving the on-surface topochemical polymerization of these carbon-rich macrocycles into tubular π-conjugated nanowires. The overall factors determining the 2D packing patterns of D24As at the liquid/solid interface are discussed on the basis of theoretical simulations, providing useful guidelines for controlling the self-assembly pattern of future D24A macrocycles.

  6. NCBI nr-aa BLAST: CBRC-ACAR-01-0270 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0270 ref|ZP_01849772.1| tungsten-containing formylmethanofuran dehydro...genase, subunit B [Methylobacterium sp. 4-46] gb|EDK91743.1| tungsten-containing formylmethanofuran dehydrogenase, subunit B [Methylobacterium sp. 4-46] ZP_01849772.1 3e-04 32% ...

  7. Fatal Chromobacterium violaceum septicaemia in northern Laos, a modified oxidase test and post-mortem forensic family G6PD analysis

    Directory of Open Access Journals (Sweden)

    Mayxay Mayfong

    2009-07-01

    Full Text Available Abstract Background Chromobacterium violaceum is a Gram negative facultative anaerobic bacillus, found in soil and stagnant water, that usually has a violet pigmented appearance on agar culture. It is rarely described as a human pathogen, mostly from tropical and subtropical areas. Case presentation A 53 year-old farmer died with Chromobacterium violaceum septicemia in Laos. A modified oxidase method was used to demonstrate that this violacious organism was oxidase positive. Forensic analysis of the glucose-6-phosphate dehydrogenase genotypes of his family suggest that the deceased patient did not have this possible predisposing condition. Conclusion C. violaceum infection should be included in the differential diagnosis in patients presenting with community-acquired septicaemia in tropical and subtropical areas. The apparently neglected but simple modified oxidase test may be useful in the oxidase assessment of other violet-pigmented organisms or of those growing on violet coloured agar.

  8. Bandagem ajustável do tronco pulmonar: IX: atividade da G6PD do miocárdio de cabras adultas submetido ao treinamento ventricular

    Directory of Open Access Journals (Sweden)

    Renato Samy Assad

    2013-12-01

    Full Text Available OBJETIVO: O aumento da atividade miocárdica da Glicose 6-Fosfato Desidrogenase tem sido demonstrado na insuficiência cardíaca. Este estudo avalia a atividade miocárdica da Glicose 6-Fosfato Desidrogenase no treinamento do ventrículo subpulmonar de cabras adultas. MÉTODOS: Foram utilizadas 18 cabras adultas, divididas em três grupos: convencional (bandagem fixa, sham e intermitente (bandagem ajustável; 12 horas diárias de sobrecarga. A sobrecarga sistólica (70% da pressão sistêmica foi mantida durante quatro semanas. As avaliações hemodinâmica e ecocardiográfica foram realizadas durante todo o estudo. Depois de cumprido o protocolo, os animais foram mortos para avaliação morfológica e da atividade da Glicose 6-Fosfato Desidrogenase dos ventrículos. RESULTADOS: Apesar de haver sobrecarga sistólica proporcionalmente menor no ventrículo subpulmonar do grupo intermitente (P=0,001, ambos os grupos de estudo apresentaram aumento da massa muscular de magnitude similar. Os grupos intermitente e convencional apresentaram aumento da massa de 55,7% e 36,7% (P<0,05, respectivamente, em comparação ao grupo sham. O conteúdo de água do miocárdio não variou entre os grupos estudados (P=0,27. O ecocardiograma demonstrou maior aumento (37,2% na espessura do ventrículo subpulmonar do grupo intermitente, em relação aos grupos sham e convencional (P<0,05. Foi observada maior atividade da Glicose 6-Fosfato Desidrogenase na hipertrofia miocárdica do ventrículo subpulmonar do grupo convencional, comparada aos grupos sham e intermitente (P=0,05. CONCLUSÃO: Ambos os grupos de treinamento ventricular desenvolveram hipertrofia ventricular, a despeito do menor tempo de sobrecarga sistólica no grupo intermitente. A maior atividade de Glicose 6-Fosfato Desidrogenase observada no grupo convencional pode refletir um desequilíbrio redox, com maior produção de fosfato de dinucleotídeo de nicotinamida e adenina e glutationa reduzida, um mecanismo importante da fisiopatologia da insuficiência cardíaca.

  9. Activity of divicine in Plasmodium vinckei-infected mice has implications for treatment of favism and epidemiology of G-6-PD deficiency.

    Science.gov (United States)

    Clark, I A; Cowden, W B; Hunt, N H; Maxwell, L E; Mackie, E J

    1984-07-01

    Intravenous injection of divicine into mice infected with Plasmodium vinckei rapidly killed the parasites and caused haemolysis. Degenerating parasites were observed frequently inside intact circulating erythrocytes, implying that parasite death was not a passive consequence of haemolysis. Both parasite death and haemolysis were prevented by the iron chelator desferrioxamine. In vitro, divicine caused the accumulation of malonyldialdehyde and the depletion of reduced glutathione in normal mouse erythrocytes. Desferrioxamine inhibited the former event, but not the latter. These observations support the hypothesis advanced by Huheey & Martin (Experientia, 31, 1145, 1975) to explain the patchy geographical distribution of glucose-6-phosphate dehydrogenase deficiency in historic malarial areas and also suggest that desferrioxamine, a drug already in clinical use, is a potential treatment for favism and other examples of oxidative haemolysis.

  10. Gibberellin biosynthesis in maize. Metabolic studies with GA{sub 15}, GA{sub 24}, GA{sub 25}, GA{sub 7}, and 2,3-dehydro-GA{sub 9}

    Energy Technology Data Exchange (ETDEWEB)

    Davis, G.; Kobayashi, Masatomo; Phinney, B.O.; Lange, T.; Croker, S.J.; Gaskin, P.; MacMillan, J.

    1999-11-01

    [17-{sup 14}C]-Labeled GA{sub 15}, GA{sub 24}, GA{sub 25}, GA{sub 7}, and 2,3-dehydro-GA{sub 9} were separately injected into normal, dwarf-1 (d1), and dwarf-5 (d5) seedlings of maize (Zea mays L.). Purified radioactive metabolites from the plant tissues were identified by sull-scan gas chromatography-mass spectrometry and Kovats retention index data. The metabolites from GA{sub 15} were GA{sub 44}, GA{sub 19}, GA{sub 20}, GA{sub 113}, and GA{sub 15}-15,16-ene (artifact?). GA{sub 24} was metabolized to GA{sub 19}, GA{sub 20}, and GA{sub 17}. The metabolites from GA{sub 25} were GA{sub 17}, GA{sub 25} 16{alpha},17-H{sub 2}-17-OH, and HO-GA{sub 25} (hydroxyl position not determined). GA{sub 7} was metabolized to GA{sub 30}, GA{sub 3}, isoGA{sub 3} (artifact?), and trace amounts of GA{sub 7}-diene-diacid (artifact?). 2,3-Dehydro-GA{sub 9} was metabolized to GA{sub 5}, GA{sub 7} (trace amounts), 2,3-dehydro-GA{sub 10} (artifact?), GA{sub 31}, and GA{sub 62}. Their results provide additional in vivo evidence of a metabolic grid in maize (i.e., pathway convergence). The grid connects members of a putative, non-early 3,130hydroxylation branch pathway to the corresponding members of the previously documented early 13-hydroxylation branch pathway. The inability to detect the sequence GA{sub 12}{r{underscore}arrow} GA{sub 15} {r{underscore}arrow} GA{sub 24} {r{underscore}arrow} GA{sub 9} indicates that the non-early 3,13-hydroxylation pathway probably plays a minor role in the origin of bioactive gibberellins in maize.

  11. A New Biochemical Way for Conversion of CO2 to Methanol via Dehydrogenases Encapsulated in SiO2 Matrix

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    CO2 is converted to methanol through an enzymatic approach using formate dehydro- genase (FateDH), formaldehyde dehydrogenase (FaldDH) and alcohol dehydrogenase (ADH) co- encapsulated in silica gel prepared by modified sol-gel process as catalysts, TEOS as precursor, NADH as an electron donor. The highest yield of methanol was up to 92.1% under 37℃, pH7.0 and 0.3Mpa.

  12. Serum lactic dehydrogenase isoenzymes and serum hydroxy butyric dehydrogenase in myocardial infarction

    Directory of Open Access Journals (Sweden)

    Kanekar D

    1979-01-01

    Full Text Available Total serum lactate dehydrogenase activity in cases of myocar-dial infarct is difficult to interpret as abnormal values can occur in diseases of liver, kidney and skeletal muscle. The estimation of its isoenzymes is of better diagnostic help because of its tissue specificity. Serum LDH isoenzymes were studied in patients o f myocardial infarction and results are quantitated by densitometry. As LDH 1 represents serum hydroxybutyric dehydrogenase when 2-oxylbutyrate is used as substrate, serum hydroxybutyric dehydro-genase was also estimated in above patients. Greater specificity in diagnosis is achieved with SHBDH because of its myocardial nature and lower incidence of false positive results.

  13. AFRRI (Armed Forces Radiobiology Research Institute) Reports, July, August and September 1986

    Science.gov (United States)

    1986-09-01

    counts, monocyte counts, relative neutrophil counts. TABLE I HEMATOLOGY Day I Day 2 Day 3 Hematocrit ( PVC ) (%) 44 ± 0.4 42 ±0.8 41 ±0.5 47 ± 1.0C...cre- atine phosphokinase (CPK), lactate dehydro- genase ( LDH ), glutamic oxaloacetic trans- aminase (SGOT), glutamic pyruvic transam- inase (SGPT...Petroleum 174 ± 14 179 ± 31 215 ± 23c Shale 209 + 32 192 ± 16 256±41c Lactate dehydrogenase ( LDH ) (lU/liter) Control 1035 ± 103 1085 ± 73

  14. 1376G→T mutation of G6PD gene in Han and Li nationalities in Hainan, China%海南汉族、黎族人群葡萄糖-6-磷酸脱氢酶基因的1376G→T突变

    Institute of Scientific and Technical Information of China (English)

    蔡望伟; 蔡兰洁; 周代锋; 邝宇; 周玉英; Filosa Stefania; Martini Giuseppe

    2000-01-01

    目的了解海南汉族、黎族人群G6PD缺乏症患者的G6PD基因1376G→T突变.方法用盐提取法提取G6PD缺乏症患者白细胞的DNA,用等位基因特异聚合酶链反应检测1376G→T突变.结果在分析的59例汉族患者和32例黎族患者中,19例汉族患者和18例黎族患者有G6PD基因1376G→T突变,该突变在汉族、黎族患者中所占的比例分别为32.2%和56.2%.结论 G6PD基因1376G→T是引起海南黎族、汉族人G6PD缺乏症的主要突变之一;根据中国不同民族的聚类分析图,该结果提示1376G→T突变可能在黎族人形成之前已经出现.研究不同民族的G6PD基因突变,对于阐明各民族的起源、迁移、进化等具有重要的意义.

  15. Immobilized Enzymes/Bacteria for Naval Applications - Initial Data Base.

    Science.gov (United States)

    1981-05-31

    donor 1.2.1.9 Glyceraldehyde phosphate dehydro- genase 1. HCIdonor 1.3.1.3 Cortisone reductase 14C-12donor 1.4.3.4 Monoamine oxidase 1.5 C-NHI donor...Q)1 " H - 4 : 0- a)4 $4 0 , gwpua0(U , W 4J A 44 >US.40 $ C UV ) d.4 wo00-4 -A.OC 4) Q-- CO rI$ - 4 J4 0W 6 $ ,UO () Q G0 4-r4 " 4 w0 -400 -W C 0 -4b0... Uv EU :> .- -J 4J -L 0 > Z C. -0~0- r4 $00)4- U042 Q)-4CU CDUUU -~ 00 0. U) I~ ~ 4’ * 78 C) Co .4 0 0w 4j ;rj 4 0 -4-4 P.-1 U) 0 . 414 $4 -’ 0> 0 $4 w

  16. Effects of Nitrogen Application on Nitrogen Metabolism Key Enzyme in Grains of Silage Maize%氮素用量对饲用玉米子粒氮代谢关键酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    于秋竹; 孔宇; 杨亮; 邹德堂

    2009-01-01

    试验以中原单32、龙辐208和高油115三个品种为材料,研究氮素用量对饲用玉米子粒氮代谢关键酶活性的影响.结果表明:饲用玉米子粒谷氨酰胺合成酶(Glutamine Synthetase,GS)和谷氨酸脱氢酶(glutamate dehydro-genase,GDH)活性在吐丝后均呈先升高后降低的变化趋势,但最大值出现时期因品种和氮素用量而异,氮素用量对子粒GS和GDH活性的影响因品种和时期而异,子粒GS和GDH(除吐丝后49d外)活性各处理间差异呈显著或极显著;子粒GDH和GS活性与生物干重呈显著或极显著正相关

  17. Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Ezzat Khodashenas

    2015-09-01

    Conclusion: Based on the findings, establishment of an early G6PD screening program, which can prevent further complications in neonates, seems essential, particularly in countries such as Iran where G6PD deficiency is highly prevalent.

  18. Glucose-6-phosphate dehydrogenase mutations and haplotypes in Mexican Mestizos.

    Science.gov (United States)

    Arámbula, E; Aguilar L, J C; Vaca, G

    2000-08-01

    In a screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 1985 unrelated male subjects from the general population (Groups A and B) belonging to four states of the Pacific coast, 21 G-6-PD-deficient subjects were detected. Screening for mutations at the G-6-PD gene by PCR-restriction enzyme in these 21 G-6-PD-deficient subjects as well as in 14 G-6-PD-deficient patients with hemolytic anemia belonging to several states of Mexico showed two common G-6-PD variants: G-6-PD A-(202A/376G) (19 cases) and G-6-PD A-(376G/968C) (9 cases). In 7 individuals the mutations responsible for the enzyme deficiency remain to be determined. Furthermore, four silent polymorphic sites at the G-6-PD gene (PvuII, PstI, 1311, and NlaIII) were investigated in the 28 individuals with G-6-PD A- variants and in 137 G-6-PD normal subjects. As expected, only 10 different haplotypes were observed. To date, in our project aiming to determine the molecular basis of G-6-PD deficiency in Mexico, 60 unrelated G-6-PD-deficient Mexican males-25 in previous studies and 35 in the present work-have been studied. More than 75% of these individuals are from states of the Pacific coast (Sinaloa, Nayarit, Jalisco, Michoacán, Guerrero, Oaxaca, and Chiapas). The results show that although G-6-PD deficiency is heterogeneous at the DNA level in Mexico, only three polymorphic variants have been observed: G-6-PD A-(202A/376G) (36 cases), G-6-PD A-(376G/968C) (13 cases), and G-6-PD Seattle(844C) (2 cases). G-6-PD A- variants are relatively distributed homogeneously and both variants explain 82% of the overall prevalence of G-6-PD deficiency. The variant G-6-PD A-(202A/376G) represents 73% of the G-6-PD A- alleles. Our data also show that the variant G-6-PD A-(376G/968C)-which has been observed in Mexico in the context of two different haplotypes-is more common than previously supposed. The three polymorphic variants that we observed in Mexico are on the same haplotypes as found in subjects from

  19. Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency in south-east Sicily.

    Science.gov (United States)

    Cittadella, R; Civitelli, D; Manna, I; Azzia, N; Di Cataldo, A; Schilirò, G; Brancati, C

    1997-05-01

    In order to explore the nature of glucose-6-phosphate dehydrogenase (G6PD) deficiency in south-east Sicily, we have analysed the G6PD gene in 25 unrelated males with abnormal G6PD activity and/or electrophoretic mobility, by using the analysis of the appropriate PCR-amplified fragment of DNA and subsequent digestion by appropriate restriction-enzymes, looking for the presence of certain known G6PD mutations. We amplified the entire G6PD coding sequence into eight fragments, followed by single-strand conformation polymorphism (SSCP) analysis and sequencing of those individual fragments that were found to be abnormal by SSCP. Through these methods we found a total of twelve G6PD Mediterranean variants with the association of a silent mutation 1311 (also known as polymorphic site Bcl I), one G6PD Mediterranean without this association, four G6PD A-Val 68 and two G6PD Santamaria and five G6PD Chatham. In a subject with normal activity a mutation was found in exon 5, designated as G6PD Sao Borja. This is the first report on the molecular analysis of G6PD mutations in Sicily and we have obtained evidence for four distinct classes of variants.

  20. Prevalence and molecular characterization of Glucose-6-Phosphate dehydrogenase deficient variants among the Kurdish population of Northern Iraq

    Directory of Open Access Journals (Sweden)

    Jamal Shakir AR

    2010-07-01

    Full Text Available Abstract Background Glucose-6-Phosphate dehydrogenase (G6PD is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds. Methods A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C→T, G6PD Chatham (1003 G→A, G6PD A- (202 G→A, G6PD Aures (143 T→C and G6PD Cosenza (1376 G→C, as well as the silent 1311 (C→T mutation. Results Among 580 random Iraqi male Kurds, 63 (10.9% had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8% had the G6PD Mediterranean variant and 10 (8.7% had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5% uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases. Conclusions The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD

  1. Glucose-6-phosphate dehydrogenase deficiency in northern Mexico and description of a novel mutation

    Indian Academy of Sciences (India)

    N. García-Magallanes; F. Luque-Ortega; E. M. Aguilar-Medina; R. Ramos-Payán; C. Galaviz-Hernández; J. G. Romero-Quintana; L. Del Pozo-Yauner; H. Rangel-Villalobos; E. Arámbula-Meraz

    2014-08-01

    Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% ($n = 1993$); the mutations in 86% of these samples were G6PD A-202A/376G, G6PD A-376G/968C and G6PD Santamaria376G/542T. Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country $(P = 0.48336)$, and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF193A>G (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described.

  2. Overexpression of glucose-6-phosphate dehydrogenase is associated with lipid dysregulation and insulin resistance in obesity.

    Science.gov (United States)

    Park, Jiyoung; Rho, Ho Kyung; Kim, Kang Ho; Choe, Sung Sik; Lee, Yun Sok; Kim, Jae Bum

    2005-06-01

    Glucose-6-phosphate dehydrogenase (G6PD) produces cellular NADPH, which is required for the biosynthesis of fatty acids and cholesterol. Although G6PD is required for lipogenesis, it is poorly understood whether G6PD in adipocytes is involved in energy homeostasis, such as lipid and glucose metabolism. We report here that G6PD plays a role in adipogenesis and that its increase is tightly associated with the dysregulation of lipid metabolism and insulin resistance in obesity. We observed that the enzymatic activity and expression levels of G6PD were significantly elevated in white adipose tissues of obese models, including db/db, ob/ob, and diet-induced obesity mice. In 3T3-L1 cells, G6PD overexpression stimulated the expression of most adipocyte marker genes and elevated the levels of cellular free fatty acids, triglyceride, and FFA release. Consistently, G6PD knockdown via small interfering RNA attenuated adipocyte differentiation with less lipid droplet accumulation. Surprisingly, the expression of certain adipocytokines such as tumor necrosis factor alpha and resistin was increased, whereas that of adiponectin was decreased in G6PD overexpressed adipocytes. In accordance with these results, overexpression of G6PD impaired insulin signaling and suppressed insulin-dependent glucose uptake in adipocytes. Taken together, these data strongly suggest that aberrant increase of G6PD in obese and/or diabetic subjects would alter lipid metabolism and adipocytokine expression, thereby resulting in failure of lipid homeostasis and insulin resistance in adipocytes.

  3. Glucose-6-Phosphate Dehydrogenase Deficiency among Male Blood Donors in Sana’a City, Yemen

    Science.gov (United States)

    Al-Nood, Hafiz A.; Bazara, Fakiha A.; Al-Absi, Rashad; Habori, Molham AL

    2012-01-01

    Objectives To determine the prevalence of Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among Yemeni people from different regions of the country living in the capital city, Sana’a, giving an indication of its overall prevalence in Yemen. Methods A cross-sectional study was conducted among Yemeni male blood donors attending the Department of Blood Bank at the National Centre of the Public Health Laboratories in the capital city, Sana’a, Yemen. Fluorescent spot method was used for screening, spectrophotometeric estimation of G-6-PD activity and separation by electrophoresis was done to determine the G-6-PD phenotype. Results Of the total 508 male blood donors recruited into the study, 36 were G-6-PD deficient, giving a likely G-6-PD deficiency prevalence of 7.1%. None of these deficient donors had history of anemia or jaundice. Thirty-five of these deficient cases (97.2%) showed severe G-6-PD deficiency class II (<10% of normal activity), and their phenotyping presumptively revealed a G-6-PD-Mediterranean variant. Conclusion The results showed a significant presence of G-6-PD deficiency with predominance of a severe G-6-PD deficiency type in these blood donors in Sana’a City, which could represent an important health problem through occurrence of hemolytic anemia under oxidative stress. A larger sample size is needed to determine the overall prevalence of G-6-PD deficiency, and should be extended to include DNA analysis to identify its variants in Yemen. PMID:22359725

  4. The Difference of Soluble Sugar Accumulation and Related Enzymes Activities in Pear Fruit from Hybrid Offspring%‘鸭梨’ב京白梨’杂交后代果实可溶性糖积累差异以及相关酶活性研究

    Institute of Scientific and Technical Information of China (English)

    杨志军; 乐文全; 张绍铃; 姚改芳; 张虎平; 马翠云; 吴俊

    2012-01-01

    以‘鸭梨’ב京白梨’杂交后代果实中分别表现高糖和低糖的个体GT-Y10和DT-Y168为试材,研究其果实发育过程中总糖、蔗糖、果糖、葡萄糖和山梨醇含量以及糖代谢相关酶活性的变化。结果表明:GT-Y10和DT-Y168中果糖含量最高,分别占总糖含量的45.77%和50.98%,山梨醇含量次之,蔗糖含量相对较低。成熟时,GT-Y10的果糖含量显著低于DT-Y168,而蔗糖、葡萄糖、山梨醇乃至总糖含量均显著高于DT-Y168。GT-Y10和DT-Y168蔗糖含量差异主要由SS(合成方向)引起;葡萄糖和果糖的差异主要由于NAD+-SDH和NADP+-SDH活性的差异引起,同时受AI、NI和SS(分解方向)的影响;NAD+-SDH和NADP+-SDH还造成山梨醇含量的差异。%Two individuals ( GT-Y10, DT-Y168 ), showing comparative higher or lower sugar content with fruit respectively, from the population of 'Yali'×' Jingbaili' were taken as materials. The contents of total sugar, sucrose, fructose, glucose, sorbitol and the activities of sugar related metabolizing enzymes were analyzed and compared. Results showed that the content of fructose in GT-Y 10 and DT-Y 168 was the highest, and accounted for 45.77% and 50.98% of total sugar content; The content of sorbitol following as the second, and the content of sucrose was comparative lower. At the stage of fruit ripening, the content of fructose in GT-Y 10 was lower than that of DT-Y168, while the content of sucrose, glucose, sorbitol were higher in contrary, and resulted in total sugar difference between GT-Y10 and DT-Y168. The key enzyme that resulted in the difference of sucrose content between GT-Y10 and DT-Y168 was the sucrose synthase (synthetic activity), the difference of glucose and fructose content between GT-+ 10 and DT-Y 168 weremainly resulted by NAD+-dependent sorbitol dehydrogenase and NADP+-dependent sorbitol dehydro- genase, meanwhile it also affected by acid

  5. 超量表达苹果酸脱氢酶基因提高苜蓿对铝毒的耐受性%Transgenic Alfalfa Plants Overexpressing Nodule-enhanced Malate Dehydrogenase Enhances Tolerance to Aluminum Toxicity

    Institute of Scientific and Technical Information of China (English)

    罗小英; 崔衍波; 邓伟; 李德谋; 裴炎

    2004-01-01

    在酸性土壤中,铝毒是许多作物正常生产的主要限制因子.虽可通过施用生石灰来改良土壤酸碱度,但只能改善土壤表层,在实际应用中受到很大限制.紫花苜蓿作为一种非常重要的牧草、饲料,在酸性土壤条件下苜蓿生长缓慢甚至死亡.我国南方水热资源丰富,但土壤多偏酸性,限制了苜蓿南移.有机酸能螯合铝离子,减轻铝对植物根系的危害.苹果酸是游离铝离子的有效螯合剂,而苹果酸脱氢酶(Malate Dehydro-genase,MDH)催化草酰乙酸形成苹果酸.本研究在苜蓿中超量表达苹果酸脱氢酶基因,通过抗生素筛选、组织化学染色和PCR扩增等技术鉴定出转化植株,并对转化株系进行了耐铝胁迫试验,比较分析了转基因株系与非转基因株系的的相对伸长量,转基因株系根相对伸长量比对照高出3.6%~22.5%.说明超量表达neMDH基因可提高了转基因苜蓿对铝毒的耐受性.

  6. A Comprehensive Selection of Reference Genes for RT-qPCR Analysis in a Predatory Lady Beetle, Hippodamia convergens (Coleoptera: Coccinellidae.

    Directory of Open Access Journals (Sweden)

    Huipeng Pan

    Full Text Available Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR is a reliable, rapid, and reproducible technique for measuring and evaluating changes in gene expression. To facilitate gene expression studies and obtain more accurate RT-qPCR data, normalization relative to stable reference genes is required. In this study, expression profiles of seven candidate reference genes, including β-actin (Actin, elongation factor 1 α (EF1A, glyceralde hyde-3-phosphate dehydro-genase (GAPDH, cyclophilins A (CypA, vacuolar-type H+-ATPase (ATPase, 28S ribosomal RNA (28S, and 18S ribosomal RNA (18S from Hippodamia convergens were investigated. H. convergens is an abundant predatory species in the New World, and has been widely used as a biological control agent against sap-sucking insect pests, primarily aphids. A total of four analytical methods, geNorm, Normfinder, BestKeeper, and the ΔCt method, were employed to evaluate the performance of these seven genes as endogenous controls under diverse experimental conditions. Additionally, RefFinder, a comprehensive evaluation platform integrating the four above mentioned algorithms, ranked the overall stability of these candidate genes. A suite of reference genes were specifically recommended for each experimental condition. Among them, 28S, EF1A, and CypA were the best reference genes across different development stages; GAPDH, 28S, and CypA were most stable in different tissues. GAPDH and CypA were most stable in female and male adults and photoperiod conditions, 28S and EF1A were most stable under a range of temperatures, Actin and CypA were most stable under dietary RNAi condition. This work establishes a standardized RT-qPCR analysis in H. convergens. Additionally, this study lays a foundation for functional genomics research in H. convergens and sheds light on the ecological risk assessment of RNAi-based biopesticides on this non-target biological control agent.

  7. A novel R198H mutation in the glucose-6-phosphate dehydrogenase gene in the tribal groups of the Nilgiris in Southern India.

    Science.gov (United States)

    Chalvam, R; Kedar, P S; Colah, R B; Ghosh, K; Mukherjee, M B

    2008-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common red cell enzymopathy among humans. In India, G6PD Mediterranean, G6PD Orissa, and G6PD Kerala-Kalyan are the three common mutations which account almost 90% of G6PD deficiency. Here we describe G6PD Coimbra, an unreported variant from India, and a novel 593 G --> A mutation in exon 6 with an amino acid change of Arg 198 His, among the tribal groups of the Nilgiris in Southern India. Further, this novel mutation was structurally characterized and it was found that the mutation is located at the end of the coenzyme domain, which may cause enzyme instability.

  8. Evaluation of Glucose-6-Phosphate Dehydrogenase Deficiency without Hemolysis in Icteric Newborns

    Directory of Open Access Journals (Sweden)

    Farzaneh Eghbalian

    2007-04-01

    Full Text Available Objective: Glucose-6- phosphate dehydrogenase (G6PD deficiency is an inherited deficiency that may be the cause of neonatal jaundice. Our aim was to study the prevalence of G6PD deficiency without hemolysis in relation to neonatal jaundice. Material & Methods: This prospective descriptive study has been conducted on 272 icteric newborns admitted to the Ekbatan Hospital from October 2002 to September 2004. The dataset included: age, sex, total and direct bilirubin, hemoglobin, reticulocyte count, blood group and Rh of mother and newborn, direct Coombs, G6PD level and the type of treatment. All data was analyzed by using statistical method. Findings: From 272 neonates, 12 neonates (4.4% were found to have G6PD deficiency. The male to female ratio was 5 to 1 (10 male and 2 female neonates. From 12 neonates with G6PD deficiency, hemolysis was seen in 5 neonates (41.7% and the rate of G6PD deficiency without hemolysis was 2.6%. There was no difference in the mean bilirubin level, hemoglobin level and also reticulocyte count between patients with G6PD deficiency and those without G6PD deficiency (p>0.05. Out of 12 patients with G6PD deficiency, 2 patients (16.7% had blood exchange transfusion. Rh and ABO incompatibility were not seen in any of the12 patients with G6PD deficiency. Conclusion: In this study the prevalence of G6PD deficiency in icteric newborns was considerably high and most of them were non hemolytic, so we recommend G6PD test as a screening program for every newborn at the time of delivery.

  9.  Glucose-6-Phosphate Dehydrogenase Deficiency among Male Blood Donors inSana’a City, Yemen

    Directory of Open Access Journals (Sweden)

    Molham AL-Habori

    2012-01-01

    Full Text Available  Objectives: To determine the prevalence of Glucose-6-phosphatedehydrogenase (G-6-PD deficiency among Yemeni people fromdifferent regions of the country living in the capital city, Sana’a,giving an indication of its overall prevalence in Yemen.Methods: A cross-sectional study was conducted among Yemenimale blood donors attending the Department of Blood Bank atthe National Centre of the Public Health Laboratories in thecapital city, Sana’a, Yemen. Fluorescent spot method was used forscreening, spectrophotometeric estimation of G-6-PD activityand separation by electrophoresis was done to determine the G-6-PD phenotype.Results: Of the total 508 male blood donors recruited into thestudy, 36 were G-6-PD deficient, giving a likely G-6-PD deficiencyprevalence of 7.1�20None of these deficient donors had history ofanemia or jaundice. Thirty-five of these deficient cases (97.2�howed severe G-6-PD deficiency class II (<10�0of normalactivity, and their phenotyping presumptively revealed a G-6-PDMediterraneanvariant.Conclusion: The results showed a significant presence of G-6-PD deficiency with predominance of a severe G-6-PD deficiencytype in these blood donors in Sana’a City, which could representan important health problem through occurrence of hemolyticanemia under oxidative stress. A larger sample size is needed todetermine the overall prevalence of G-6-PD deficiency, and shouldbe extended to include DNA analysis to identify its variants in Yemen.

  10. Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency in eastern indonesian populations

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    Tantular,Indah S.

    2010-12-01

    Full Text Available We conducted a field survey of glucose-6-phosphate dehydrogenese (G6PD deficiency in the eastern Indonesian islands, and analyzed G6PD variants molecularly. The incidence of G6PD deficiency in 5 ethnic groups (Manggarai, Bajawa, Nage-Keo, Larantuka, and Palue on the Flores and Palue Islands was lower than that of another native group, Sikka, or a nonnative group, Riung. Molecular analysis of G6PD variants indicated that 19 cases in Sikka had a frequency distribution of G6PD variants similar to those in our previous studies, while 8 cases in Riung had a different frequency distribution of G6PD variants. On the other hand, from field surveys in another 8 ethnic groups (Timorese, Sumbanese, Savunese, Kendari, Buton, Muna, Minahasa, and Sangirese on the islands of West Timor, Sumba, Sulawesi, Muna and Bangka, a total of 49 deficient cases were detected. Thirty-nine of these 49 cases had G6PD Vanua Lava (383T>C of Melanesian origin. In our previous studies, many cases of G6PD Vanua Lava were found on other eastern Indonesian islands. Taken together, these findings may indicate that G6PD Vanua Lava is the most common variant in eastern Indonesian populations, except for Sikka.

  11. Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency in eastern Indonesian populations.

    Science.gov (United States)

    Tantular, Indah S; Matsuoka, Hiroyuki; Kasahara, Yuichi; Pusarawati, Suhintam; Kanbe, Toshio; Tuda, Josef S B; Kido, Yasutoshi; Dachlan, Yoes P; Kawamoto, Fumihiko

    2010-12-01

    We conducted a field survey of glucose-6-phosphate dehydrogenese (G6PD) deficiency in the eastern Indonesian islands, and analyzed G6PD variants molecularly. The incidence of G6PD deficiency in 5 ethnic groups (Manggarai, Bajawa, Nage-Keo, Larantuka, and Palue) on the Flores and Palue Islands was lower than that of another native group, Sikka, or a nonnative group, Riung. Molecular analysis of G6PD variants indicated that 19 cases in Sikka had a frequency distribution of G6PD variants similar to those in our previous studies, while 8 cases in Riung had a different frequency distribution of G6PD variants. On the other hand, from field surveys in another 8 ethnic groups (Timorese, Sumbanese, Savunese, Kendari, Buton, Muna, Minahasa, and Sangirese) on the islands of West Timor, Sumba, Sulawesi, Muna and Bangka, a total of 49 deficient cases were detected. Thirty-nine of these 49 cases had G6PD Vanua Lava (383T>C) of Melanesian origin. In our previous studies, many cases of G6PD Vanua Lava were found on other eastern Indonesian islands. Taken together, these findings may indicate that G6PD Vanua Lava is the most common variant in eastern Indonesian populations, except for Sikka.

  12. Design of peptides with alpha,beta-dehydro residues: pseudo-tripeptide N-benzyloxycarbonyl-DeltaLeu-L-Ala-L-Leu-OCH3.

    Science.gov (United States)

    Makker, Jyoti; Dey, Sharmistha; Kumar, Pravindra; Singh, Tej P

    2002-04-01

    The title peptide N-benzyloxycarbonyl-DeltaLeu-L-Ala-L-Leu-OCH(3) [methyl N-(benzyloxycarbonyl)-alpha,beta-dehydroleucyl-L-alanyl-L-leucinate], C(24)H(35)N(3)O(6), was synthesized in the solution phase. The peptide adopts a type II' beta-turn conformation which is stabilized by an intramolecular 4 --> 1 N-H* * *O hydrogen bond. The crystal packing is stabilized by two intermolecular N-H* * *O hydrogen bonds.

  13. Crystal structure of N-(tert-but-oxy-carbon-yl)glycyl-(Z)-β-bromo-dehydro-alanine methyl ester [Boc-Gly-(β-Br)((Z))ΔAla-OMe].

    Science.gov (United States)

    Lenartowicz, Paweł; Makowski, Maciej; Zarychta, Bartosz; Ejsmont, Krzysztof

    2014-12-01

    The title compound, C11H17BrN2O5, is a de-hydro-amino acid with a C=C bond between the α- and β-C atoms. The amino acid residues are linked trans to each other and there are no strong intra-molecular hydrogen bonds. The torsion angles indicate a non-helical conformation of the mol-ecule. The dipeptide folding is influenced by an inter-molecular N-H⋯O hydrogen bond and also minimizes steric repulsion. In the crystal, mol-ecules are linked by strong N-H⋯O hydrogen bonds, generating (001) sheets. The sheets are linked by weak C-H⋯O and C-H⋯Br bonds and short Br⋯Br [3.4149 (3) Å] inter-actions.

  14. Hydrogen Effect on Coke Removal and Catalytic Performance in Pre-Carburization and Methane Dehydro-Aromatization Reaction on Mo/HZSM-5

    Institute of Scientific and Technical Information of China (English)

    Hongtao Ma; Ryoichi Kojima; Satoshi Kikuchi; Masaru Ichikawa

    2005-01-01

    In this study,the effects of pre-carburization of catalyst,hydrogen addition to methane feed and the space velocity of methane on the catalytic performance in methane to benzene (MTB) reaction were discussed in detail over Mo/HZSM-5 catalyst at 1023 K and 0.3 MPa. Compared with the non-precarburized catalyst,the Mo catalyst pre-carburized under the flow of CH4+4H2 at 973 K was found to have the higher activity and better stability. Further 6% H2 addition to the methane feed suppressed the aromatic type of coke formation effectively,and improved the stability of catalyst markedly,moreover gave a much longer reaction life of catalyst (53 h at 1023 K and 5400 ml/(g·h)) and much more formation amounts of benzene and hydrogen. With increase of methane space velocity,both the naphthalene formation selectivity and the coke formation selectivity were decreased by the shortened contact time;the benzene formation selectivity and total formation amount before the complete deactivation of catalyst were increased ly,while the total naphthalene and coke formation amounts did not change much.At high methane space velocity (≥5400 ml/(g·h)),a new middle temperature coke derived from the high temperature aromatic coke was formed on the catalyst; all the coke formed could be burnt off at lower temperature in oxygen,compared with those obtained at low space velocity. Considering the benzene formation amount and catalyst stability together,5400 ml/(g·h) was proved to be the most efficient methane space velocity for benzene production.

  15. Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Alfonso, Lloyd F; Marimuthu, Srinivasan; Bhat, G Jayarama

    2016-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT‑29 colorectal cancer cells, in order to compare aspirin‑mediated acetylation of G6PD and its activity between HCT 116 and HT‑29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT‑29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin‑acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH.

  16. Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the Achang population of southwestern China

    Institute of Scientific and Technical Information of China (English)

    YANG YinFeng; ZHU YueChun; LI DanYi; LI ZhiGang; L(U) HuiRu; WU Jing; TANG Jing; TONG ShuFen

    2007-01-01

    The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its gene mutations were studied in the Achang population from Lianghe County in Southwestern China. We found that 7.31%(19 of 260) males and 4.35% (10 of 230) females had G6PD deficiency. The molecular analysis of G6PD gene exons 2-13 was performed by a PCR-DHPLC-Sequencing or PCR-Sequencing. Sixteen independent subjects with G6PD Mahidol (487G>A) and the new polymorphism IVS5-612 (G>C), which combined into a novel haplotype, were identified accounting for 84.2% (16/19). And 100% Achang G6PD Mahidol were linked to the IVS5-612 C. The percentage of G6PD Mahidol in the Achang group is close to that in the Myanmar population (91.3% 73/80), which implies that there are some gene flows between Achang and Myanmar populations. Interestingly, G6PD Canton (1376G>T) and G6PD Kaiping(1388G>A), which were the most common G6PD variants from other ethnic groups in China, were not found in this Achang group, suggesting that there are different G6PD mutation profiles in the Achang group and other ethnic groups in China. Our findings appear to be the first documented report on the G6PD genetics of the AChang people, which will provide important clues to the Achang ethnic group origin and will help prevention and treatment of malaria in this area.

  17. Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the Achang population of southwestern China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its gene mutations were studied in the Achang population from Lianghe County in Southwestern China. We found that 7.31% (19 of 260) males and 4.35% (10 of 230) females had G6PD deficiency. The molecular analysis of G6PD gene exons 2―13 was performed by a PCR-DHPLC-Sequencing or PCR-Sequencing. Sixteen inde-pendent subjects with G6PD Mahidol (487G>A) and the new polymorphism IVS5-612 (G>C), which combined into a novel haplotype, were identified accounting for 84.2% (16/19). And 100% Achang G6PD Mahidol were linked to the IVS5-612 C. The percentage of G6PD Mahidol in the Achang group is close to that in the Myanmar population (91.3% 73/80), which implies that there are some gene flows between Achang and Myanmar populations. Interestingly, G6PD Canton (1376G>T) and G6PD Kaiping (1388G>A), which were the most common G6PD variants from other ethnic groups in China, were not found in this Achang group, suggesting that there are different G6PD mutation profiles in the Achang group and other ethnic groups in China. Our findings appear to be the first documented report on the G6PD genetics of the AChang people, which will provide important clues to the Achang ethnic group origin and will help prevention and treatment of malaria in this area.

  18. Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity.

    Science.gov (United States)

    Ham, Mira; Choe, Sung Sik; Shin, Kyung Cheul; Choi, Goun; Kim, Ji-Won; Noh, Jung-Ran; Kim, Yong-Hoon; Ryu, Je-Won; Yoon, Kun-Ho; Lee, Chul-Ho; Kim, Jae Bum

    2016-09-01

    Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. © 2016 by the American Diabetes Association.

  19. Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart

    Science.gov (United States)

    In the failing heart, NADPH oxidase and uncoupled NO synthase utilize cytosolic NADPH to form superoxide. NADPH is supplied principally by the pentose phosphate pathway, whose rate-limiting enzyme is glucose 6-phosphate dehydrogenase (G6PD). Therefore, we hypothesized that cardiac G6PD activation dr...

  20. Red Algal Bromophenols as Glucose 6-Phosphate Dehydrogenase Inhibitors

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    Koretaro Takahashi

    2013-10-01

    Full Text Available Five bromophenols isolated from three Rhodomelaceae algae (Laurencia nipponica, Polysiphonia morrowii, Odonthalia corymbifera showed inhibitory effects against glucose 6-phosphate dehydrogenase (G6PD. Among them, the symmetric bromophenol dimer (5 showed the highest inhibitory activity against G6PD.

  1. Modulation of nuclear T3 binding by T3 in a human hepatocyte cell-line (Chang-liver) - T3 stimulation of cell growth but not of malic enzyme, glucose-6-phosphatdehydrogenase or 6-phosphogluconate-dehydrogenase

    DEFF Research Database (Denmark)

    Matzen, L E; Kristensen, S R; Kvetny, J

    1991-01-01

    The T3 modulation of nuclear T3 binding (NBT3), the T3 effect on cell growth, and the T3 and insulin effects on malic enzyme (ME), glucose-6-phosphat-dehydrogenase (G6PD) and 6-phosphogluconat-dehydrogenase (G6PD) were studied in a human hepatocyte cell-line (Chang-liver). T3 was bound to a high...

  2. Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency in the neonatal period.

    Science.gov (United States)

    Keihanian, F; Basirjafari, S; Darbandi, B; Saeidinia, A; Jafroodi, M; Sharafi, R; Shakiba, M

    2017-06-01

    Considering the high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among newborns, different screening methods have been established in various countries. In this study, we aimed to assess the prevalence of G6PD deficiency among newborns in Rasht, Iran, and compare G6PD activity in cord blood samples, using quantitative and qualitative tests. This cross-sectional, prospective study was performed at five largest hospitals in Rasht, Guilan Province, Iran. The screening tests were performed for all the newborns, referred to these hospitals. Specimens were characterized in terms of G6PD activity under ultraviolet light, using the kinetic method and the qualitative fluorescent spot test (FST). We also determined the sensitivity, specificity, negative predictive value, and positive predictive value of the qualitative assay. Blood samples were collected from 1474 newborns. Overall, 757 (51.4%) subjects were male. As the findings revealed, 1376 (93.4%) newborns showed normal G6PD activity, while 98 (6.6%) had G6PD deficiency. There was a significant difference in the mean G6PD level between males and females (P = 0.0001). Also, a significant relationship was detected between FST results and the mean values obtained in the quantitative test (P < 0.0001). According to the present study, FST showed acceptable sensitivity and specificity for G6PD activity, although it appeared inefficient for diagnostic purposes in some cases. © 2017 John Wiley & Sons Ltd.

  3. Prevalence of glucose-6-phosphate dehydrogenase deficiency and diagnostic challenges in 1500 immigrants in Denmark examined for haemoglobinopathies

    DEFF Research Database (Denmark)

    Warny, Marie; Klausen, Tobias Wirenfeldt; Petersen, Jesper

    2015-01-01

    Similar to the thalassaemia syndromes, glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in areas historically exposed to malaria. In the present study, we used quantitative and molecular methods to determine the prevalence of G6PD deficiency in a population of 1508 immigran...

  4. Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2016-05-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I, Vanua-Lava (Class II and Viangchan (Class II. For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT. Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site.

  5. Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Serrano-Posada, Hugo; González-Valdez, Abigail; Martínez-Rosas, Víctor; Hernández-Ochoa, Beatriz; Sierra-Palacios, Edgar; Castillo-Rodríguez, Rosa Angélica; Cuevas-Cruz, Miguel; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I), Vanua-Lava (Class II) and Viangchan (Class II). For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT). Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site. PMID:27213370

  6. assessment of the activity of glucose-6-phosphate dehydrogenase ...

    African Journals Online (AJOL)

    Uwaifoh

    2012-10-31

    Oct 31, 2012 ... activity of G-6-PD was determined in type 2 diabetes mellitus patients and control subjects ... that reason, monitoring of G-6-PD activity may be an important tool in preventing diabetic injury due to ... ingestion of certain drugs or food (eg fava beans) or .... Festus OO., supervised this study with the assistance.

  7. Identification of point mutations in Glucose-6-Phosphate Dehydrogenase gene in Timor Island people : A preliminary report

    Directory of Open Access Journals (Sweden)

    Widanto Hardjowasito

    2001-12-01

    Full Text Available Glucose 6 phosphate dehydrogenase (G6PD deficiency is common in malaria endemic region, however no molecular study has been performed on G6PD deficiency in Timor Island, Indonesia a malarial hyperendemic area which Proto Malay is the majority of the people in that island. To observe the frequency and molecular type of mutations in G6PD deficient Proto Malay people, 118 native people were screened using formazan ring test. Mutation in the G6PD gene were determined by MPTP (Multiple PCR using Multiple Tandem Forward Primers and a common Reserve Pimer method and confirmed by automatic sequencer. This study shows that three males have lower G6PD activity. Using MPTP method, a point mutation could be indicated in the two cases. Sequencing of the amplified products in 2 G6PD patients disclosed mutations of T383C in exon 5 and C 592 T in exon 6 in respective case. Our result documents point mutations in exon 5 and exon 6 in the G6PD gene of two Proto Malay people in Timor. These mutations are common in Asia region. (Med J Indones 2001; 10: 210-3Keywords: mutations, G6PD, Proto Malay.

  8. Rapid screening for glucose-6-phosphate dehydrogenase deficiency and haemoglobin polymorphisms in Africa by a simple high-throughput SSOP-ELISA method

    DEFF Research Database (Denmark)

    Enevold, Anders; Vestergaard, Lasse S; Lusingu, John

    2005-01-01

    BACKGROUND: Mutations in the haemoglobin beta-globin (HbB) and glucose-6-phosphate dehydrogenase (G6PD) genes cause widespread human genetic disorders such as sickle cell diseases and G6PD deficiency. In sub-Saharan Africa, a few predominant polymorphic variants of each gene account for a majority...

  9. Features and outcomes of malaria infection in glucose-6-phosphatedehydrogenase normal and deficient Nigerian children

    Directory of Open Access Journals (Sweden)

    Adebola Emmanuel Orimadegun

    2014-01-01

    Full Text Available Background & objectives: Malaria and G6PD deficiency-related haemolyses are known causes of hospital admissions in Nigeria and pose great danger to child survival but data on interactions of these two pathologies are scarce. This study was carried out to determine the association between features of Plasmodium falciparum infection and G6PD status. Methods: G6PD and haemoglobin were typed by fluorescent spot test and electrophoresis respectively, in 1120 children with microscopically-proven falciparum malaria. Clinical features of malaria were compared between G6PD normal and deficient children. Results: There were 558 males and 562 females with median age of 35 months (range, 6 months-12 yr. In males, prevalence of G6PD-deficiency in patients with uncomplicated malaria (UM, severe malarial anaemia (SMA and cerebral malaria (CM was 23.4, 7 and 16.7%, respectively compared with 11.1, 7.3 and 4.4%, respectively among females. In both males and females, convulsion and rectal temperature above 38°C were less likely presentations among G6PD-deficient compared with G6PD-normal children (p <0.05. The proportions of children with pallor, convulsion and impaired consciousness were significantly lower among G6PD-deficient than normal males (p <0.05 but these features were not different between deficient and normal females (p >0.05. Interpretation & conclusion: Convulsions, pallor and elevated temperature were more frequent features of malaria in G6PD normal than deficient children. G6PD-deficient male children are protected against impaired consciousness. These differences may offer useful hints in malaria treatment and researches in endemic regions.

  10. Diversity in expression of glucose-6-phosphate dehydrogenase deficiency in females.

    Science.gov (United States)

    Abdulrazzaq, Y M; Micallef, R; Qureshi, M; Dawodu, A; Ahmed, I; Khidr, A; Bastaki, S M; Al-Khayat, A; Bayoumi, R A

    1999-01-01

    The aims of this study were to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe the different mutations in the population, to determine its prevalence, and to study inheritance patterns in families of G6PD-deficient individuals. All infants born at Tawam Hospital, Al-Ain, UAE from January 1994 to September 1996 were screened at birth for their G6PD status. In addition, those attending well-baby clinics during the period were also screened for the disorder. Families of 40 known G6PD-deficient individuals, selected randomly from the records of three hospitals in the country, were assessed for G6PD deficiency. Where appropriate, this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%), comprising 15% of males and 5% of females tested, were found to be G6PD deficient. A total of 27 families were further assessed: of these, all but one family had the nt563 Mediterranean mutation. In one family, two individuals had the nt202 African mutation. The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD-deficient gene and X-inactivation of the normal gene, and/or to the presence of an 'enhancer' gene that makes the expression of the G6PD deficiency more likely. The high level of consanguinity which, theoretically, should result in a high proportion of homozygotes and consequently a higher proportion of females with the deficiency, was not found to be a significant factor.

  11. Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

    Directory of Open Access Journals (Sweden)

    Olatundun Williams

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5% followed by those Igbo descent (10.6% and those of Igede (10.2% and Tiv (1.8% ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females. Yoruba children had a higher prevalence (16.9% than Igede (10.5%, Igbo (10.1% and Tiv (5.0% children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500. The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively. Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351. In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

  12. 西方蜜蜂四个亚种酯酶同工酶型和苹果酸脱氢酶Ⅱ同工酶基因型的遗传差异%GENETIC DIFFERENCES IN PATTERNS OF EST ISOZYMES AND GENOTYPES OF MDH Ⅱ ISOZYMES IN FOUR SUBSPECIES OF APIS MELLIFERA

    Institute of Scientific and Technical Information of China (English)

    童富淡; 汪俏梅; 刘艳荷

    2002-01-01

    @@ 同工酶是一组催化功能相同,分子组成和分子结构不同的酶,它由染色体上不同基因座的基因或同一基因座的等位基因编码,广泛用于昆虫种属鉴定和遗传变异研究.蜜蜂幼虫或蛹中的苹果酸脱氢酶(malate dehydrogenase,MDH)、苹果酸酶(malatese,ME)、酯酶(esterase,EST)(Shep-pard et al.,1984)、乙醇脱氢酶(alcoho dehydro-genase,ADH)(Gartside,1980)、外肽酶(exopep-tidase,EPEP)(Lama et al.,1984)和普通蛋白-3(protein-3,P-3)(Mestriner et al.,1972)的基因具有多态性.蜜蜂属(Apis)EST同工酶由一对共显性等位基因编码(Mestriner et al.,1972),不同种之间的同工酶型差异显著(李绍文等,1986).西方蜜蜂MDHⅡ的等电点位于pH6.7~7.5范围内,由a、b和c三个基因编码,能稳定遗传且无组织和发育特异性,对蜜蜂种内鉴定、遗传变异和亲缘关系的确定很有价值(Rozal-ski et al.,1996).本实验采用薄层聚丙烯酰胺凝胶等电聚焦电泳(IEF-PAGE)技术,测定了喀尔巴阡蜂(A.mellifera carpatica)、东北黑蜂(A.mellifera ssp.)、浙农大Ⅰ号意蜂(A.melliferaligustica)和卡尼鄂拉蜂(A.mellifera carnica)的EST和MDHⅡ同工酶,分析了MDHⅡ同工酶基因型频率、基因频率、纯合度和杂合度及其遗传差异,为蜜蜂的品种选育、种属鉴定和遗传变异的研究提供基础资料.

  13. Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Serrano-Posada, Hugo; Ortega-Cuellar, Daniel; González-Valdez, Abigail; Castillo-Rodríguez, Rosa Angélica; Hernández-Ochoa, Beatriz; Sierra-Palacios, Edgar; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the pentose phosphate pathway which produces nicotinamide adenine dinucleotide phosphate (NADPH) to maintain an adequate reducing environment in the cells and is especially important in red blood cells (RBC). Given its central role in the regulation of redox state, it is understandable that mutations in the gene encoding G6PD can cause deficiency of the protein activity leading to clinical manifestations such as neonatal jaundice and acute hemolytic anemia. Recently, an extensive review has been published about variants in the g6pd gene; recognizing 186 mutations. In this work, we review the state of the art in G6PD deficiency, describing 217 mutations in the g6pd gene; we also compile information about 31 new mutations, 16 that were not recognized and 15 more that have recently been reported. In order to get a better picture of the effects of new described mutations in g6pd gene, we locate the point mutations in the solved three-dimensional structure of the human G6PD protein. We found that class I mutations have the most deleterious effects on the structure and stability of the protein. PMID:27941691

  14. Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Enríquez-Flores, Sergio; De la Mora-De la Mora, Ignacio; González-Valdez, Abigail; García-Torres, Itzhel; Martínez-Rosas, Víctor; Sierra-Palacios, Edgar; Lazcano-Pérez, Fernando; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency), and the G6PD Santa Maria and A+ (less severe deficiency) (Class I, II and III, respectively) affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients. PMID:26633385

  15. Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Filosa, S.; Giacometti, N.; Wangwei, C.; Martini, G. [Istituto Internazionale di Genetica e Biofisica, Naples (Italy)] [and others

    1996-10-01

    X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G{r_arrow}A) and two with G6PD Bari (1187C{r_arrow}T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. 65 refs., 6 figs., 3 tabs.

  16. A new paper-based analytical device for detection of Glucose-6-phosphate dehydrogenase deficiency.

    Science.gov (United States)

    Kaewarsa, Phuritat; Laiwattanapaisal, Wanida; Palasuwan, Attakorn; Palasuwan, Duangdao

    2017-03-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic haemolytic disorder. Most persons with G6PD deficiency are asymptomatic, but exposure to oxidant drugs, such as the anti-malarial drug primaquine, may induce haemolysis, which is commonly found in Asian countries. A reliable test is necessary for diagnosing the deficiency to prevent an acute haemolytic crisis. This study proposes a novel quantitative method to detect G6PD deficiency using paper-based analytical devices (G6PDD-PAD). Wax printing was utilized for fabricating circular reaction zone patterns in paper. The colorimetric assay is based on the formation of formazan via a reduction of tetra-nitro blue tetrazolium (TNBT) by the G6PD enzyme on G6PDD-PAD. Detection was achieved by capturing the colour using a desktop scanner and the colour intensity was analysed with Adobe Photoshop C56. The results showed that the G6PD activity analysed by G6PDD-PAD was highly correlated with the standard biochemical assay (SBA) (r(2)=0.87, pPAD and the SBA (mean bias 1.4 IU/gHb). The detection limit was 0 IU/gHb of G6PD activity. This study demonstrates the feasibility of using G6PDD-PAD. This simple, low-cost test ($0.1/test) should be useful for diagnosing G6PD deficiency in resource-limited settings.

  17. Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2015-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency, and the G6PD Santa Maria and A+ (less severe deficiency (Class I, II and III, respectively affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients.

  18. Prevalência da deficiência da glicose-6-fosfato desidrogenase em doadores de sangue de Mossoró, Rio Grande do Norte Prevalence of glucose-6-phosphate dehydrogenase deficiency in blood donors of Mossoró, Rio Grande do Norte

    Directory of Open Access Journals (Sweden)

    Ulysses Madureira Maia

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common human enzymopathy. It affects as many as 330 million individuals worldwide. This deficiency may determine neonatal jaundice, chronic nonspherocytic hemolytic anemia and acute hemolytic anemia induced by drugs, infections and broad bean ingestion. The efficacy of blood transfusion is decreased when the donor is G6PD deficient. In this study, we aimed at determining the prevalence of G6PD deficiency in blood donors of Mossoro, Brazil. Samples of 714 blood donors (576 men and 138 women; 343 white and 371 non-white with ages ranging from 18 to 62 years and that accepted to participate in the study were analyzed. All participants answered a standard questionnaire. G6PD activity was analyzed by the methemoglobin reduction test with deficiency being confirmed by the semiquantitative test. The overall prevalence of G6PD deficiency in blood donors was 3.8%, similar to the rate described for others regions of Brazil. There was no significant statistical difference in the frequency of G6PD deficiency between men and women, nor between white and non-white blood donors. This relatively high frequency of G6PD deficiency highlights a need to screen blood donors for this condition.

  19. Contribution of haemolysis to jaundice in Sephardic Jewish glucose-6-phosphate dehydrogenase deficient neonates.

    Science.gov (United States)

    Kaplan, M; Vreman, H J; Hammerman, C; Leiter, C; Abramov, A; Stevenson, D K

    1996-06-01

    We determined the contribution of haemolysis to the development of hyperbilirubinaemia in glucose-6-phosphate dehydrogenase (G-6-PD) deficient neonates and G-6-PD normal controls. Blood carboxyhaemoglobin (COHb), sampled on the third day of life, was measured by gas chromatography, corrected for inhaled carbon monoxide (COHbC), and expressed as a percentage of total haemoglobin concentration (Hb). Serum bilirubin was tested as clinically necessary. 37 non-jaundiced (peak serum total bilirubin (PSTB) or = 257 mumol/l) G-6-PD-deficient neonates were compared to 31 non-jaundiced and 24 jaundiced controls with comparable PSTB values, respectively. COHbC values for the entire G-6-PD deficient group were higher than in the controls (0.75 +/- 0.17% v 0.62 +/- 0.19%, P 0.05) but did in the controls (r = 0.58, P < 0.001). COHbC values were increased to a similar extent in the G-6-PD-deficient, non-jaundiced (0.72 +/- 0.16%), the G-6-PD-deficient, jaundiced (0.80 +/- 0.19%) and the control, jaundiced (0.75 +/- 0.18%) subgroups, compared to the control, non-jaundiced subgroup (0.53 +/- 0.13%) (P < 0.05). Although present in G-6-PD deficient neonates, increased haemolysis was not directly related to the PSTB.

  20. Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2016-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is a key regulatory enzyme in the pentose phosphate pathway which produces nicotinamide adenine dinucleotide phosphate (NADPH to maintain an adequate reducing environment in the cells and is especially important in red blood cells (RBC. Given its central role in the regulation of redox state, it is understandable that mutations in the gene encoding G6PD can cause deficiency of the protein activity leading to clinical manifestations such as neonatal jaundice and acute hemolytic anemia. Recently, an extensive review has been published about variants in the g6pd gene; recognizing 186 mutations. In this work, we review the state of the art in G6PD deficiency, describing 217 mutations in the g6pd gene; we also compile information about 31 new mutations, 16 that were not recognized and 15 more that have recently been reported. In order to get a better picture of the effects of new described mutations in g6pd gene, we locate the point mutations in the solved three-dimensional structure of the human G6PD protein. We found that class I mutations have the most deleterious effects on the structure and stability of the protein.

  1. Definitive localization of intracellular proteins: Novel approach using CRISPR-Cas9 genome editing, with glucose 6-phosphate dehydrogenase as a model.

    Science.gov (United States)

    Spencer, Netanya Y; Yan, Ziying; Cong, Le; Zhang, Yulong; Engelhardt, John F; Stanton, Robert C

    2016-02-01

    Studies to determine subcellular localization and translocation of proteins are important because subcellular localization of proteins affects every aspect of cellular function. Such studies frequently utilize mutagenesis to alter amino acid sequences hypothesized to constitute subcellular localization signals. These studies often utilize fluorescent protein tags to facilitate live cell imaging. These methods are excellent for studies of monomeric proteins, but for multimeric proteins, they are unable to rule out artifacts from native protein subunits already present in the cells. That is, native monomers might direct the localization of fluorescent proteins with their localization signals obliterated. We have developed a method for ruling out such artifacts, and we use glucose 6-phosphate dehydrogenase (G6PD) as a model to demonstrate the method's utility. Because G6PD is capable of homodimerization, we employed a novel approach to remove interference from native G6PD. We produced a G6PD knockout somatic (hepatic) cell line using CRISPR-Cas9 mediated genome engineering. Transfection of G6PD knockout cells with G6PD fluorescent mutant proteins demonstrated that the major subcellular localization sequences of G6PD are within the N-terminal portion of the protein. This approach sets a new gold standard for similar studies of subcellular localization signals in all homodimerization-capable proteins.

  2. Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border.

    Directory of Open Access Journals (Sweden)

    Qing Li

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage. G6PD deficiency is particularly prevalent in historically malaria-endemic areas. Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients. In this study, we systematically evaluated the prevalence of G6PD deficiency in the Kachin (Jingpo ethnic group along the China-Myanmar border and determined the underlying G6PD genotypes. We surveyed G6PD deficiency in 1770 adult individuals (671 males and 1099 females of the Kachin ethnicity using a G6PD fluorescent spot test. The overall prevalence of G6PD deficiency in the study population was 29.6% (523/1770, among which 27.9% and 30.6% were males and females, respectively. From these G6PD deficient samples, 198 unrelated individuals (147 females and 51 males were selected for genotyping at 11 known G6PD single nucleotide polymorphisms (SNPs in Southeast Asia (ten in exons and one in intron 11 using a multiplex SNaPshot assay. Mutations with known association to a deficient phenotype were detected in 43.9% (87/198 of cases, intronic and synonymous mutations were detected alone in 34.8% (69/198 cases and no mutation were found in 21.2% (42/198 cases. Five non-synonymous mutations, Mahidol 487G>A, Kaiping 1388G>A, Canton 1376G>T, Chinese 4 392G>T, and Viangchan 871G>A were detected. Of the 87 cases with known deficient mutations, the Mahidol variant was the most common (89.7%; 78/87, followed by the Kaiping (8.0%; 7/87 and the Viangchan (2.2%; 2/87 variants. The Canton and Chinese 4 variants were found in 1.1% of these 87 cases. Among them, two females carried the Mahidol/Viangchan and Mahidol/Kaiping double mutations, respectively. Interestingly, the silent SNPs 1311C>T and IVS11nt93T>C both occurred in the same 95 subjects with frequencies at 56.4% and 23.5% in tested females and males, respectively (PT/IVS11nt93T>C SNPs

  3. Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

    Directory of Open Access Journals (Sweden)

    Ruth Owusu

    Full Text Available Sulphadoxine-Pyrimethamine (SP is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp.Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women.The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia.There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger

  4. Effect of mercuric acetate on selected enzymes of maternal and fetal hamsters at different gestational ages

    Energy Technology Data Exchange (ETDEWEB)

    Karp, W.B.; Gale, T.F.; Subramanyam, S.B.; DuRant, R.H.

    1985-04-01

    This study establishes levels of activity of glucose-6-phosphate dehydrogenase (G6PD), glycogen phosphorlyase (GP), and cytochrome c oxidase (cyt c ox) in maternal, placental, and fetal tissues at Days 9, 12, and 15 in the 16-day gestation period of the hamster, and following a single dose of either 8 or 15 mg/kg mercuric acetate on the eighth gestational day. Mercury significantly elevated maternal kidney G6PD activity and decreased GP activity. The increase in kidney G6PD strongly correlated with observed urine and kidney abnormalities.

  5. Metoclopramide

    Science.gov (United States)

    ... pressure; depression; breast cancer; asthma;glucose-6-phosphate dehydrogenase (G-6PD) deficiency (an inherited blood disorder); NADH ... ask your doctor about the safe use of alcohol while you are taking this medication. Alcohol can ...

  6. Nitrofurantoin

    Science.gov (United States)

    ... lung disease, nerve damage, or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (an inherited blood disease). ... ask your doctor about the safe use of alcohol while you are taking this medication. Alcohol can ...

  7. Flutamide

    Science.gov (United States)

    ... inherited blood diseases such as glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or hemoglobin M disease. ... flutamide. Flutamide may cause facial flushing, and drinking alcohol can make it worse.

  8. Blue cures blue but be cautious

    Directory of Open Access Journals (Sweden)

    Pranav Sikka

    2011-01-01

    Full Text Available Methemoglobinemia is a disorder characterized by the presence of >1% methemoglobin (metHb in the blood. Spontaneous formation of methemoglobin is normally counteracted by protective enzyme systems, for example, nicotinamide adenine dinucleotide phosphate (NADPH methemoglobin reductase. Methemoglobinemia is treated with supplemental oxygen and methylene blue (1-2 mg/kg administered slow intravenously, which acts by providing an artificial electron acceptor for NADPH methemoglobin reductase. But known or suspected glucose-6-phosphate dehydrogenase (G6PD deficiency is a relative contraindication to the use of methylene blue because G6PD is the key enzyme in the formation of NADPH through pentose phosphate pathway and G6PD-deficient individuals generate insufficient NADPH to efficiently reduce methylene blue to leukomethylene blue, which is necessary for the activation of the NADPH-dependent methemoglobin reductase system. So, we should be careful using methylene blue in methemoglobinemia patient before G6PD levels.

  9. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition in which ...

  10. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that helps red ...

  11. Associations between red cell polymorphisms and Plasmodium falciparum infection in the middle belt of Ghana

    National Research Council Canada - National Science Library

    Amoako, Nicholas; Asante, Kwaku Poku; Adjei, George; Awandare, Gordon A; Bimi, Langbong; Owusu-Agyei, Seth

    2014-01-01

    .... In a cross-sectional study of 341 febrile children less than five years of age, associations between clinical malaria and common RBC polymorphisms including the sickle cell gene and G6PD deficiency...

  12. Prevalence of glucose-6-phosphate dehydrogenase deficiency and haemoglobin S in high and moderate malaria transmission areas of Muheza, north-eastern Tanzania

    DEFF Research Database (Denmark)

    Segeja, M D; Mmbando, Bruno Paul; Kamugisha, M L;

    2008-01-01

    by the disease. In November-December 2003, we conducted a cross-sectional survey to determine the prevalence of G6PD deficiency and HbS in the population and relate these to malaria infection and haemoglobin levels in lowland and highland areas of differing malaria transmission patterns of Muheza, Tanzania...... prevalence of G6PD deficiency and HbS than highlands (G6PD deficiency = 11.32% (24/212) versus 4.43% (9/203), P = 0.01, and HbS = 16.04% (98/611) versus 6.32% (36/570), P = 0.0001). Logistic regression model showed an association between G6PD deficiency and altitude [lowlands] (Odds ratio [OR] 3.4, 95% CI...

  13. Prevalence of glucose-6-phosphate dehydrogenase deficiency in ...

    African Journals Online (AJOL)

    Pradeep Kumar

    2016-02-06

    Feb 6, 2016 ... for studies that investigated G6PD deficiency in Indian population. If any author studied .... analyses, (2) case reports, and (3) reviews and editorials. 2.3. ..... Beutler E, editors. Glucose-6-phosphate dehydrogenase. Orlando,.

  14. DETECTION OF OCCULT GLOMERULAR DYSFUNCTION IN GLUCOSE SIX PHOSPHATE DEHYDROGENASE DEFICIENCY ANEMIA

    Directory of Open Access Journals (Sweden)

    Gehan Abdel Hakeem

    2016-08-01

    G6PD deficiency anemia is associated with a variable degree of glomerular dysfunction during acute hemolytic episodes. This glomerular dysfunction can result in chronic subclinical or occult chronic kidney injury.

  15. Glucose-6-phosphate-dehydrogenase deficiency and its correlation with other risk factors in jaundiced newborns in Southern Brazil

    Institute of Scientific and Technical Information of China (English)

    Clarissa Gutirrez Carvalho; Simone Martins Castro; Ana Paula Santin; Carina Zaleski; Felipe Gutirrez Carvalho; Roberto Giugliani

    2011-01-01

    Objective:To evaluate the correlation between glucose-6-phosphate-dehydrogenase (G6PD) deficiency and neonatal jaundice.Methods: Prospective, observational case-control study was conducted on490 newborns admitted to Hospital de Clínicas de Porto Alegre for phototherapy, who all experienced35 or more weeks of gestation, from March to December2007. Enzymatic screening ofG6PD activity was performed, followed byPCR.Results:There was prevalence of4.6% and a boy-girl ratio of3:1 in jaundiced newborns. No jaundiced neonate withABO incompatibility presented G6PD deficiency, and no Mediterranean mutation was found. A higher proportion of deficiency was observed in Afro-descendants. There was no association withUGT1A1 variants. Conclusions:G6PD deficiency is not related to severe hyperbilirubinemia and considering the high miscegenation in this area of Brazil, other gene interactions should be investigated.

  16. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency.

    Science.gov (United States)

    Kaplan, M; Rubaltelli, F F; Hammerman, C; Vilei, M T; Leiter, C; Abramov, A; Muraca, M

    1996-05-01

    We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

  17. Hemolysis Induced by Glucose-6-Phosphate Dehydrogenase Deficiency and Its Association with Sex in Children

    Directory of Open Access Journals (Sweden)

    Esmaeel Sadeghi

    2010-03-01

    Full Text Available Background: Glucose-6-phosphate dehydrogenase (G6PDdeficiency is the most common enzyme disorder in human.The aim of this study was to determine the prevalence ofG6PD deficiency among children and evaluate its associationwith ABO/Rh blood groups.Method: Blood samples of 3401 asymptomatic children wereanalyzed and compared with 317 children who were admitted tohospital because of hemolysis resulted fromG6PD deficiency.Results: Among asymptomatic children 375 (11% were G6PDdeficient. Male to female ratio for this group was 4.2:1 and forthe hemolytic group was 2.5:1 (P=0.004. Two hundred andsixty-seven (84.2% of the patients with hemolysis wereyounger than 2 years, with the peak age of hemolysis between 2and 3 years (27.7%. The overall rate of hemolysis caused byG6PD deficiency was 12.3% during the 3 consecutive monthsof fresh Fava bean consumption. Blood groups O+, A+, and B+together constituted 87.1%, 87.7%, and 84% of the bloodgroups among normal children, asymptomatic G6PD deficientsubjects, and those with G6PD deficiency related hemolysisrespectively (P=0.367. Seven percent of the normal childrenand asymptomatic G6PD deficient subjects were Rh- vs 9.7 %of G6PD deficient children with hemolysis (P=0.16.Conclusion: The prevalence of G6PD deficiency among thechildren was 11%. Male to female ratio was greater in nonhemolyticvs hemolytic group so that the female share was higherin hemolytic group than in the other two groups (P=0.004.The distribution of ABO blood groups was similar amongasymptomatic non-G6PD deficient, asymptomatic G6PDdeficient,and G6PD-deficient children with hemolysis. Thedistribution of Rh- types among the G6PD-deficient childrenwith hemolysis and the other two groups was similar (9.7% vs7%, P=0.16.

  18. Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group.

    Science.gov (United States)

    Thriemer, Kamala; Ley, Benedikt; Bobogare, Albino; Dysoley, Lek; Alam, Mohammad Shafiul; Pasaribu, Ayodhia P; Sattabongkot, Jetsumon; Jambert, Elodie; Domingo, Gonzalo J; Commons, Robert; Auburn, Sarah; Marfurt, Jutta; Devine, Angela; Aktaruzzaman, Mohammad M; Sohel, Nayeem; Namgay, Rinzin; Drukpa, Tobgyel; Sharma, Surender Nath; Sarawati, Elvieda; Samad, Iriani; Theodora, Minerva; Nambanya, Simone; Ounekham, Sonesay; Mudin, Rose Nanti Binti; Da Thakur, Garib; Makita, Leo Sora; Deray, Raffy; Lee, Sang-Eun; Boaz, Leonard; Danansuriya, Manjula N; Mudiyanselage, Santha D; Chinanonwait, Nipon; Kitchakarn, Suravadee; Nausien, Johnny; Naket, Esau; Duc, Thang Ngo; Do Manh, Ha; Hong, Young S; Cheng, Qin; Richards, Jack S; Kusriastuti, Rita; Satyagraha, Ari; Noviyanti, Rintis; Ding, Xavier C; Khan, Wasif Ali; Swe Phru, Ching; Guoding, Zhu; Qi, Gao; Kaneko, Akira; Miotto, Olivo; Nguitragool, Wang; Roobsoong, Wanlapa; Battle, Katherine; Howes, Rosalind E; Roca-Feltrer, Arantxa; Duparc, Stephan; Bhowmick, Ipsita Pal; Kenangalem, Enny; Bibit, Jo-Anne; Barry, Alyssa; Sintasath, David; Abeyasinghe, Rabindra; Sibley, Carol H; McCarthy, James; von Seidlein, Lorenz; Baird, J Kevin; Price, Ric N

    2017-04-05

    The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by  the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.

  19. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This stud...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

  20. Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity

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    Dallol Ashraf

    2012-09-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 deficiency is caused by one or more mutations in the G6PD gene on chromosome X. An association between enzyme levels and gene haplotypes remains to be established. Methods In this study, we determined G6PD enzyme levels and sequenced the coding region, including the intron-exon boundaries, in a group of individuals (163 males and 86 females who were referred to the clinic with suspected G6PD deficiency. The sequence data were analysed by physical linkage analysis and PHASE haplotype reconstruction. Results All previously reported G6PD missense changes, including the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our cohort. The AURES mutation (p.Ile48Thr was the most common variant in the cohort (30% in males patients followed by the Mediterranean variant (p.Ser188Phe detectable in 17.79% in male patients. Variant forms of the A- mutation (p.Val68Met, p.Asn126Asp or a combination of both were detectable in 15.33% of the male patients. However, unique to this study, several of such mutations co-existed in the same patient as shown by physical linkage in males or PHASE haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD, 13 different haplotypes (13 in males, 8 in females were identified. Five of these were previously unreported (Jeddah A, B, C, D and E and were defined by previously unreported combinations of extant mutations where patients harbouring these haplotypes exhibited severe G6PD deficiency. Conclusions Our findings will help design a focused population screening approach and provide better management for G6PD deficiency patients.

  1. Establishment of an In Vitro Assay for Assessing the Effects of Drugs on the Liver Stages of Plasmodium vivax Malaria

    Science.gov (United States)

    2010-06-01

    caused by P. falciparum, some recent studies reported severe symptoms and signs, including death , due to Pv infection [5,6]. It is also reported that...screening for G6PD deficiency must be done before administration. Also, as the G6PD status of the unborn fetus cannot be determined easily, primaquine is...and death than does P. falciparum, but is more widespread globally and infects 80–300 million people every year [3]. Unlike the other major human

  2. Incidence and molecular characterization of Glucose-6-Phosphate Dehydrogenase deficiency among neonates for newborn screening in Chaozhou, China.

    Science.gov (United States)

    Yang, H; Wang, Q; Zheng, L; Zhan, X-F; Lin, M; Lin, F; Tong, X; Luo, Z-Y; Huang, Y; Yang, L-Y

    2015-06-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in southern China. The aim of this study is to assess the extent of this disease in Chinese neonates and determine its molecular characteristics using a novel molecular screening method. A total of 2500 neonates were routinely screened for G6PD deficiency using a modified fluorescent spot test (FST). PCR-high-resolution melting (HRM) analysis was then used for the molecular assay. The overall incidence of G6PD deficiency was 2.68% in our study cohort. Frequency in male population was 3.22% (44 neonates of 1365 male neonates), and in female population was 2.03% (23 neonates of 1135 female neonates). Of the 67 newborns suspected to be G6PD deficient based on FST (44 males, 23 females), 58 of 67 (87%) were detected with gene alterations. Seven kinds of mutations [c.95A>G, c.392G>T, c.493A>G, c.871G>A, c.1360C>T, c.1376G>T, and c.1388G>A] were identified by HRM analysis. Routine newborn screening in Chaozhou, China with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation. The usage of molecular diagnosis can favor the detection of heterozygotes which can be a supplement to regular newborn screening and useful for premarital and prenatal diagnosis for G6PD deficiency. © 2014 John Wiley & Sons Ltd.

  3. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study

    Science.gov (United States)

    Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

    2015-01-01

    Summary Background The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. Methods We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3–12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. Findings 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant

  4. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali.

    Science.gov (United States)

    Maiga, Bakary; Dolo, Amagana; Campino, Susana; Sepulveda, Nuno; Corran, Patrick; Rockett, Kirk A; Troye-Blomberg, Marita; Doumbo, Ogobara K; Clark, Taane G

    2014-07-11

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males

  5. Determinação da acurácia do método qualitativo da medida da atividade da glicose-6-fosfato desidrogenase Determination of the accuracy of the measurement method for dehydrogenase activity

    Directory of Open Access Journals (Sweden)

    Letícia L. Giovelli

    2007-12-01

    Full Text Available A deficiência de glicose-6-fosfato desidrogenase (G6PD é um problema de saúde pública que afeta aproximadamente 400 milhões de pessoas no mundo. No mercado, existem vários métodos que medem a atividade da G6PD. Os objetivos deste estudo foram determinar a acurácia do método de Brewer frente a um padrão de referência e estimar a prevalência de deficiência de G6PD na amostra. Foi realizado um estudo transversal de grupo de pacientes internados no HCPA com icterícia a esclarecer, no período de junho de 2004 a maio de 2005. Amostras foram processadas pelo método de Brewer e pelo método de Normalização da Hemoglobina, o qual foi usado como padrão ouro. Foi analisado para atividade da G6PD um total de 173 pacientes. A idade variou de 1 dia a 82 anos, sendo que 66% da amostra possuía até 15 dias de vida. A atividade média e o desvio padrão da G6PD na amostra analisada foi de 17.67± 5,66 U/gHb. A freqüência estimada, pelo padrão ouro, da deficiência de G6PD, foi de 13 (7,7% pacientes com deficiência parcial ou total, e pelo método de Brewer foi de 14 (8,67%. A sensibilidade do método de Brewer comparada com o método quantitativo da Normalização da Hemoglobina foi de 92,8% e a especificidade foi de 98,7%. A deficiência de G6PD é prevalente em nosso meio. Testes de baixo custo, tais como o teste de Brewer, podem ser utilizados como testes de triagem desta deficiência, principalmente no monitoramento de recém-nascidos que estão sob o risco de desenvolver icterícia neonatal.Glucose-6-phosphate dehydrogenase deficiency (G6PD is a public health problem which affects about 400 millions of people all over the world. Some methods that measure the activity of G6PD have already been developed. Thus, the aim of this study was to evaluate the accuracy of the Brewer's method compared with a standard reference and estimate the prevalence of G6PD deficiency in the sample. A cross-sectional study of a group of patients in HCPA

  6. Erythrocyte glucose-6-phosphate dehydrogenase from Brazilian opossum Didelphis marsupialis

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    Barretto O.C. de O.

    2006-01-01

    Full Text Available In a comparative study of erythrocyte metabolism of vertebrates, the specific activity of glucose-6-phosphate dehydrogenase (G6PD of the Brazilian opossum Didelphis marsupialis in a hemolysate was shown to be high, 207 ± 38 IU g-1 Hb-1 min-1 at 37ºC, compared to the human erythrocyte activity of 12 ± 2 IU g-1 Hb-1 min-1 at 37ºC. The apparent high specific activity of the mixture led us to investigate the physicochemical properties of the opossum enzyme. We report that reduced glutathione (GSH in the erythrocytes was only 50% higher than in human erythrocytes, a value lower than expected from the high G6PD activity since GSH is maintained in a reduced state by G6PD activity. The molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was 265 kDa, which is essentially the same as that of human G6PD (260 kDa. The Michaelis-Menten constants (Km: 55 µM for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (Km: 3.3 µM were similar to those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively. A 450-fold purification of the opossum enzyme was achieved and the specific activity of the purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein observed for human G6PD. We conclude that G6PD after purification from the hemolysate of D. marsupialis does not have a high specific activity. Thus, it is quite probable that the red cell hyperactivity reported may be explained by increased synthesis of G6PD molecules per unit of hemoglobin or to reduced inactivation in the RBC hemolysate.

  7. A novel c.197T ® A variant among Brazilian neonates with glucose-6-phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    José Pereira de Moura Neto

    2008-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 deficiency is the most common enzyme deficiency worldwide, causing a spectrum of diseases including neonatal hyperbilirubinemia and acute or chronic hemolysis. We used the methemoglobin reduction test and G6PD electrophoresis to screen 655 neonates (354 females and 301 males for common G6PD mutations in the city of Salvador in the Northeastern Brazilian state Bahia and found that 66 (10.1% were G6PD-deficient (41 females and 25 males. The 66 (10.1% G6PD-deficient neonates were assessed for the c.376 A -> G (exon 5 and c.202 G -> A (exon 4 mutations using the polymerase chain reaction and restriction enzyme fragment length polymorphism (PCR-RFLP analysis and the results validated by DNA sequencing. Of the 66 G6PD-deficient neonates investigated we found that 54 (81.8% presented the c.376 A -> G (p.Asn126Asp and c.202 G -> A (p.Val68Met mutations, two (3% had the c.376 A -> G mutation only, two (3% had the c.202 G -> A mutation only, five (7.6% exhibited a previously unrecorded 197T -> A (p.Phe66Thr substitution in exon 4 and three showed no mutations at any of these sites. Of the five neonates exhibiting the new 197T -> A (p.Phe66Thr substitution, four (6.1% also presented the c.202 G -> A and c.376 A -> G mutations and one (1.5% had the c.[197T -> A / 202 G -> A] combination. We propose to name the new variant G6PD Bahia.

  8. Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling

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    Yi-Hsuan Wu

    2015-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α and GTPase myxovirus resistance 1 (MX1—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E and enterovirus 71 (EV71 infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP+ ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG.

  9. [Frequency of glucose-6-phosphate dehydrogenase deficiency (A-376/202) in three Malian ethnic groups].

    Science.gov (United States)

    Dolo, A; Maiga, B; Guindo, A; Diakité, S A S; Diakite, M; Tapily, A; Traoré, M; Sangaré, B; Arama, C; Daou, M; Doumbo, O

    2014-08-01

    Erythrocyte G6PD deficiency is the most common worldwide enzymopathy. The aim of this study was to determine erythrocyte G6PD deficiency in 3 ethnic groups of Mali and to investigate whether erythrocyte G6PD deficiency was associated to the observed protection against malaria seen in Fulani ethnic group. The study was conducted in two different areas of Mali: in the Sahel region of Mopti where Fulani and Dogon live as sympatric ethnic groups and in the Sudanese savannah area where lives mostly the Malinke ethnic group. The study was conducted in 2007 in Koro and in 2008 in Naguilabougou. It included a total 90 Dogon, 42 Fulani and 80 Malinke ethnic groups. Malaria was diagnosed using microscopic examination after Giemsa-staining of thick and thin blood smear. G6PD deficiency (A-(376/202)) samples were identified using RFLP (Restriction Fragment Length Polymorphism) assay and analysis of PCR-amplified DNA amplicon. G6PD deficiency (A-(376/202)) rate was 11.1%, 2.4%, and 13.3% in Dogon, Fulani, and Malinke ethnic group respectively. Heterozygous state for G6PD (A-(376/202)) was found in 7.8% in Dogon; 2.4% in Fulani and 9.3% in Malinke ethnic groups while hemizygous state was found at the frequency of 2.2% in Dogon and 4% in Malinke. No homozygous state was found in our study population.We conclude that G6PD deficiency is not differing significantly between the three ethnic groups, Fulani, Dogon and Malinke.

  10. Comparative analysis of glucose-6-phosphate dehydrogenase levels in pre-term and term babies delivered at University of Ilorin Teaching Hospital, Nigeria

    Directory of Open Access Journals (Sweden)

    Temitope Olorunsola Obasa

    2012-03-01

    Full Text Available Glucose-6-phosphate (G6P is an enzyme in the hexose monophosphate shunt required for the production of reducing equivalents needed to mop up free radicals. thereby keeping hemoglobin in its free state. Deficiency of the enzyme can cause severe neonatal jaundice. The aim of this study was to compare G6PD levels in pre-term and term babies, and evaluate the extent to which G6PD deficiency determines the severity of jaundice in various gestational age groups. Samples of cord blood collected from consecutively delivered babies in the University of Ilorin Teaching Hospital, Nigeria, were assayed for G6PD levels, and the babies were observed for jaundice during the first week of life. Those who developed jaundice had serial serum bilirubin measured. Nine hundred and thirty-three babies had G6PD assayed, with 348 being G6PD deficient, giving a hospital based prevalence of 37.3%. Of the 644 who were followed up, 143 (22.2% were pre-term and 501(77.8% were term babies. Babies with gestational age (GA 27-29 weeks had the highest G6PD levels. However, there was no significant variation among the different gestational age groups (F=0.64, P=0.64. Jaundice occurred more in pre-term compared to term babies with a relative risk of 2.41 (χ2=60.95, P=0.00001. Occurrence of jaundice in pre-term babies was irrespective of G6PD status (χ2=0.2, P=0.66, RR=1.09, CI=0.83

  11. Glucose-6-phosphate dehydrogenase deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2.

    Science.gov (United States)

    Roshankhah, Shiva; Rostami-Far, Zahra; Shaveisi-Zadeh, Farhad; Movafagh, Abolfazl; Bakhtiari, Mitra; Shaveisi-Zadeh, Jila

    2016-12-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as H2O2. We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of H2O2, which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility. Semen samples were obtained from four males with G6PD deficiency and eight healthy males as a control. In both groups, motile sperms were isolated from the seminal fluid and incubated with 0, 10, 20, 40, 60, 80, and 120 µM concentrations of H2O2. After 1 hour incubation at 37℃, sperms were evaluated for motility and viability. Incubation of sperms with 10 and 20 µM H2O2 led to very little decrease in motility and viability, but motility decreased notably in both groups in 40, 60, and 80 µM H2O2, and viability decreased in both groups in 40, 60, 80, and 120 µM H2O2. However, no statistically significant differences were found between the G6PD-deficient group and controls. G6PD deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2, and the reducing equivalents necessary for protection against H2O2 are most likely produced by other pathways. Therefore, G6PD deficiency cannot be considered as major risk factor for male infertility.

  12. Evaluation of the blue formazan spot test for screening glucose 6 phosphate dehydrogenase deficiency.

    Science.gov (United States)

    Pujades, A; Lewis, M; Salvati, A M; Miwa, S; Fujii, H; Zarza, R; Alvarez, R; Rull, E; Corrons, J L

    1999-06-01

    Several screening tests for glucose 6 phosphate dehydrogenase (G6PD) deficiency have been reported thus far, and a standardized method of testing was proposed by the International Council for Standardization in Hematology (ICSH). The screening test used in any particular laboratory depends upon a number of factors such as cost, time required, temperature, humidity, and availability of reagents. In this study, a direct comparison between three different G6PD screening methods has been undertaken. In 71 cases (50 hematologically normal volunteers, 9 hemizygous G6PD-deficient males, and 12 heterozygous deficient females), the blue formazan spot test (BFST) was compared with the conventional methemoglobin reduction test (HiRT) and the ICSH-recommended fluorescent spot test (FST-ICSH). In all cases, the results obtained with the three screening tests were correlated with the enzyme activity assayed spectrophotometrically. In hemizygous G6PD-deficient males, all cases were equally detected with the three methods: BFST (4.7-6.64, controls: 11.1-13.4), BMRT (score +3 in all 9 cases), and FST (no fluorescence in 9 cases). In heterozygous G6PD-deficient females, two methods detected 7 out of 12 cases (BFST: 8.71-11.75, controls: 11.1-13.4; and BMRT: score +3 in 7 cases), whereas the FST-ICSH missed all 12 cases that presented a variable degree of fluorescence. Although the sensitivity for G6PD-deficient carrier detection is the same for the BMRT and the BFST, the latter has the advantage of being semiquantitative and not merely qualitative. Unfortunately, none of the three screening tests compared here allowed the detection of the 100% heterozygote carrier state of G6PD deficiency.

  13. Pyrrolizidine and tropane alkaloids in teas and the herbal teas peppermint, rooibos and chamomile in the Israeli market.

    Science.gov (United States)

    Shimshoni, Jakob Avi; Duebecke, Arne; Mulder, Patrick P J; Cuneah, Olga; Barel, Shimon

    2015-01-01

    Dehydro pyrrolizidine alkaloids (dehydro PAs) are carcinogenic phytotoxins prevalent in the Boraginaceae, Asteraceae and Fabaceae families. Dehydro PAs enter the food and feed chain by co-harvesting of crops intended for human and animal consumption as well as by carry-over into animal-based products such as milk, eggs and honey. Recently the occurrence of dehydro PAs in teas and herbal teas has gained increasing attention from the EU, due to the high levels of dehydro PAs found in commercially available teas and herbal teas in Germany and Switzerland. Furthermore, several tropane alkaloids (TAs, e.g. scopolamine and hyoscyamine) intoxications due to the consumption of contaminated herbal teas were reported in the literature. The aim of the present study was to determine the dehydro PAs and TAs levels in 70 pre-packed teabags of herbal and non-herbal tea types sold in supermarkets in Israel. Chamomile, peppermint and rooibos teas contained high dehydro PAs levels in almost all samples analysed. Lower amounts were detected in black and green teas, while no dehydro PAs were found in fennel and melissa herbal teas. Total dehydro PAs concentrations in chamomile, peppermint and rooibos teas ranged from 20 to 1729 μg/kg. Except for black tea containing only mono-ester retrorsine-type dehydro PAs, all other teas and herbal teas showed mixed patterns of dehydro PA ester types, indicating a contamination by various weed species during harvesting and/or production. The TA levels per teabag were below the recommended acute reference dose; however, the positive findings of TAs in all peppermint tea samples warrant a more extensive survey. The partially high levels of dehydro PAs found in teas and herbal teas present an urgent warning letter to the regulatory authorities to perform routine quality control analysis and implement maximum residual levels for dehydro PAs.

  14. Deficiencia de glucosa 6-fostato deshidrogenasa en hombres sanos y en pacientes maláricos; Turbo (Antioquia, Colombia Deficiency of glucose-6-phosphate dehydrogenase in healthy men and malaria patients; Turbo (Antioquia, Colombia

    Directory of Open Access Journals (Sweden)

    Jaime Carmona-Fonseca

    2008-06-01

    Full Text Available INTRODUCCIÓN: En América Latina la deficiencia de glucosa 6-fosfato deshidrogenasa (d-G6PD ha sido poco estudiada y en Colombia solo conocemos tres publicaciones antiguas. Urge conocer más la prevalencia de d-G6PD, sobre todo ahora que el tratamiento de la malaria vivax plantea aumentar la dosis diaria o total de primaquina. OBJETIVO: Medir la prevalencia de d-G6PD en poblaciones masculina sana y de enfermos con malaria por Plasmodium vivax, en Turbo (Urabá, departamento de Antioquia, Colombia. METODOLOGÍA: Encuestas de prevalencia, para evaluar la G6PD en dos poblaciones de Turbo (Antioquia: hombres sanos; hombres y mujeres con malaria vivax. Se trabajó con muestras diseñadas con criterios estadístico-epidemiológicos. La actividad enzimática se midió con el método normalizado de Beutler para valorar la G6PD en hemolizados. RESULTADOS: Entre los hombres sanos (n = 508, el intervalo de confianza 95% para el promedio (IC95% estuvo entre 4,15 y 4,51 UI/g hemoglobina y 14,8% presentaron valores por debajo del "límite normal" de INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD deficiency in Latin America has not been fully studied and in Colombia only three outdated publications are known. Recent information on the prevalence of G6PD deficiency is required now, because the recommended treatment of vivax malaria requires higher daily or total doses of primaquine. OBJECTIVE: To measure the prevalence of G6PD in a healthy male population and in a Plasmodium vivax infected population in Turbo (Urabá, Antioquia Department, Colombia. METHOD: Prevalence survey to evaluate G6PD in two populations of Turbo (Antioquia: healthy male; male and female with vivax malaria. The work was carried out on population samples selected using statistical and epidemiological criteria. Enzyme activity was measured using Beutler's normalized method to evaluate G6PD after hemolysis. RESULTS: For the healthy male group (n = 508, and with a 95% confidence

  15. False-Positive Newborn Screen Using the Beutler Spot Assay for Galactosemia in Glucose-6-Phosphate Dehydrogenase Deficiency.

    Science.gov (United States)

    Stuhrman, Grace; Perez Juanazo, Stefanie J; Crivelly, Kea; Smith, Jennifer; Andersson, Hans; Morava, Eva

    2017-01-12

    Classical galactosemia is detected through newborn screening by measuring galactose-1-phosphate uridylyltransferase (GALT) in the USA primarily via the Beutler spot assay. We report on an 18-month-old patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency that was originally diagnosed with classical galactosemia. The patient presented with elevated liver function enzymes and bilirubinemia and was immediately treated with soy-based formula. Confirmatory tests revealed deficiency of the GALT enzyme, however, full-sequencing of GALT was normal, suggestive of a different ideology. The Beutler spot assay uses three other enzymatic steps in addition to GALT. A deficiency in either of these enzymes can result in suspected decreased GALT activity when using the Beutler assay. Congenital Disorders of Glycosylation screening for phosphoglucomutase-1 deficiency was negative. Quantitative analysis of G6PD enzyme in red blood cells showed a severe deficiency and a deletion in G6PD. Soy-formula, the standard treatment for galactosemia, has been reported to trigger hemolysis in G6PD deficient patients. G6PD and phosphoglucomutase-1 deficiencies should be considered when confirmatory tests are negative for pathogenic variants in GALT and galactose-1-phosphate level is normal.

  16. Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study

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    S Matsubara

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of the present study was to investigate the subcellular localization of G6PD in alveolar cells in the rat lung using a newly- developed enzyme-cytochemistry (copper-ferrocyanide method. Type I cells and stromal endothelia and fibroblasts showed no activities. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of type II alveolar epithelial cells. The cytochemical controls ensured specific detection of enzyme activity. This enzyme may play a role in airway defense by delivering substances for cell proliferation and antioxidant forces, thus maintaining the airway architecture.

  17. Advances in the Molecular Biological Research of Human Glucose-6-phosphate Dehydrogenase%人类葡萄糖-6-磷酸脱氢酶的分子生物学研究进展

    Institute of Scientific and Technical Information of China (English)

    刘晗; 蒋玮莹

    2009-01-01

    葡萄糖-6-磷酸脱氢酶(glucose-6-phosphate dehydrogenase,G6PD)缺乏症作为一种全球范围内最常见的酶缺乏症之一,受到研究者们的广泛关注.G6PD催化磷酸戊糖途径的第一步,由此酶催化生成的NADPH+H+对于对抗氧化性损伤是极其重要的.本文将从G6PD的结构与功能,SNP的研究与单体型的建立,抗疟疾选择优势与新的G6PD基因突变检测方法这几方面的研究进展综述如下.%Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most common enzymopathies attracting many researchers.G6PD catalyses the first committed step in the pentose phosphate pathway,and the generation of NADPH by this enzyme is essential for protection against oxidative stress.The progress in research of the structures and functions of G6PD gene'S,SNP and haplotype,new detective techniques of new mutation and recent positive selection of anti-malaria are reviewed.

  18. Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency.

    Science.gov (United States)

    LaRue, Nicole; Kahn, Maria; Murray, Marjorie; Leader, Brandon T; Bansil, Pooja; McGray, Sarah; Kalnoky, Michael; Zhang, Hao; Huang, Huiqiang; Jiang, Hui; Domingo, Gonzalo J

    2014-10-01

    A barrier to eliminating Plasmodium vivax malaria is inadequate treatment of infected patients. 8-Aminoquinoline-based drugs clear the parasite; however, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for hemolysis from these drugs. Understanding the performance of G6PD deficiency tests is critical for patient safety. Two quantitative assays and two qualitative tests were evaluated. The comparison of quantitative assays gave a Pearson correlation coefficient of 0.7585 with significant difference in mean G6PD activity, highlighting the need to adhere to a single reference assay. Both qualitative tests had high sensitivity and negative predictive value at a cutoff G6PD value of 40% of normal activity if interpreted conservatively and performed under laboratory conditions. The performance of both tests dropped at a cutoff level of 45%. Cytochemical staining of specimens confirmed that heterozygous females with > 50% G6PD-deficient cells can seem normal by phenotypic tests. © The American Society of Tropical Medicine and Hygiene.

  19. Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition

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    Kinoshita Ayako

    2005-05-01

    Full Text Available Abstract Background Cell simulation, which aims to predict the complex and dynamic behavior of living cells, is becoming a valuable tool. In silico models of human red blood cell (RBC metabolism have been developed by several laboratories. An RBC model using the E-Cell simulation system has been developed. This prototype model consists of three major metabolic pathways, namely, the glycolytic pathway, the pentose phosphate pathway and the nucleotide metabolic pathway. Like the previous model by Joshi and Palsson, it also models physical effects such as osmotic balance. This model was used here to reconstruct the pathology arising from hereditary glucose-6-phosphate dehydrogenase (G6PD deficiency, which is the most common deficiency in human RBC. Results Since the prototype model could not reproduce the state of G6PD deficiency, the model was modified to include a pathway for de novo glutathione synthesis and a glutathione disulfide (GSSG export system. The de novo glutathione (GSH synthesis pathway was found to compensate partially for the lowered GSH concentrations resulting from G6PD deficiency, with the result that GSSG could be maintained at a very low concentration due to the active export system. Conclusion The results of the simulation were consistent with the estimated situation of real G6PD-deficient cells. These results suggest that the de novo glutathione synthesis pathway and the GSSG export system play an important role in alleviating the consequences of G6PD deficiency.

  20. Glucose 6-phosphate dehydrogenase on indian piaroas in malaria-endemic area.

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    Gilberto Antonio Bastidas-Pacheco

    2017-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD remains intact sulfhydryl groups and assist in the detoxification of free radicals and peroxides, therefore deficit irreversible oxidative damage and destruction of the erythrocyte when these are subjected to oxidative substances and stress. Plasmodium spp. infection causes anemia as a result of the rupture of the erythrocyte by this parasite, it can be aggravated in people infected with G6PD deficiency when exposed to drugs. Descriptive field study in which the enzymatic activity of G6PD in an indigenous community of Piaroa municipality of Atures Amazonas state was determined by biochemical tests. The sample consisted of 186 individuals, 100 women and 86 men. The average concentration of hemoglobin was 10.6 g/dL, 88, 6% of the subjects were moderately anemic and none had G6PD deficiency. It is concluded that anemia is common in indigenous Piaroas, moderate and deficiency type; no biochemical test that G6PD deficiency is detected; and that this study provides useful information to state agencies responsible for administering health care in Venezuela information.

  1. Efeito da temperatura, pH e vestígios de Hg2+ e Pb2+ na acti­vidade de desidrogenases e urease num solo da região de Évora Effect of temperature, pH and Hg2+ and Pb2+ traces in dehydrogenaseand urease activities of a soil from Évora region

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    M. R. Martins

    2010-01-01

    Full Text Available As actividades das enzimas no solo são um importante indicador da sua qualida­de. Neste estudo procedeu-se à caracteri­zação da actividade enzimática de desi­drogenases (EC 1.1.1 e da urease (EC 3.5.1.5 de um solo sob Olea europeae L. da região de Évora. As constantes cinéti­cas Km e Vmáx, foram determinadas usando como substratos o cloreto de p­-iodonitrotetrazolio (INT e a ureia, res­pectivamente. Foi avaliado o efeito nas referidas actividades provocado pelo pH, temperatura e vestígios de Hg2+ e de Pb2+. As actividades máximas obtiveram-se a pH = 8,5 e 40 ºC, com Km= 0,5 mM e Vmáx = 5,4 µmol min-1 g-1, para a activida­de de desidrogenases e a pH = 10 e 37 ºC, com Km = 25,7 mM e Vmáx = 2,0x10-2 µmol min-1 g-1, para a urease. Estas acti­vidades foram inibidas por diferentes concentrações de Hg2+, mas apenas a acti­vidade da urease foi inibida pelo Pb2+. Estes resultados são comparáveis com os referidos na literatura para estes enzimas.Enzyme activities are often used as in­dicator of soil quality. This study reports on dehydrogenase (EC 1.1.1 and urease (EC 3.5.1.5 activities of a soil under Olea europaea L. from Évora region. Kinetic constants Km and Vmax were determined using p-iodonitrotetrazolium chloride (INT and urea, respectively. Effects of pH, temperature and Hg2+ and Pb2+ traces on both activities were determined. Maximal activity was obtained at pH = 8.5 and 40ºC, Km = 0.5 mM and Vmax=5,4µmol min-1 g-1 , for dehydro­genase and at pH = 10 and 37 ºC, Km = 25.7 mM and Vmax = 2.0x10-2 µmol min-1 g-1, for urease. These activities were in­hibited by different concentrations of Hg2+, but only the urease activity was in­hibited by Pb2+. Results of this study are comparable to those reported in the litera­ture for these enzymes.

  2. Construction of differentially expressed cDNA libraries of aldehyde dehydrogenase with high and low activity from tongue squamous carcinoma Tca8113 cell line%基于舌鳞癌Tca8113细胞醛脱氢酶活性不同构建差异表达基因cDNA文库

    Institute of Scientific and Technical Information of China (English)

    孙守娟; 季平; 邓诚; 李颖; 邹波; 漆小娟

    2012-01-01

    Objective To construct the differentially expressed cDNA libraries of aldehyde dehydro genase with high and low activity (ALDHhigh/ALDHlow) from tongue squamous carcinoma Tca8113 cell line. Methods Expression of stem cell marker ALDH was detected, and ALDHhighand ALDHlow cells were collected by Aldefluor assay combined with flow cytometry. Differentially expressed genes of total RNA that was extracted from the two cell subpopulations by Trizol were screened and amplified by suppressing subtractive hybridization ( SSH) , and the PCR products were connected with pMD18-T vector and then transfected into E. Coli DH5a for amplification. Enzyme digestion, gene sequencing and homology analysis were performed in 24 positive clones that were randomly picked from each library. Results Two subproportions of ALDHhigh and ALDHlowwere " screened out, and ALDHhigh cells in Tca8113 cells accounted for 2. 5%. RNA D(260)/D(280) of ALDHhigh and ALDHlow were 1. 93 and 1. 92, respectively. Two-directional subtractive cDNA libraries of ALDHhigh and ALDHlow were constructed, and each library comprised 500 clones. PCR analysis of 24 clones randomly picked from each library showed that insert-fragments distributed in 200 - 700 bp, and no false positive clones were detected. Gene sequencing result that was analyzed and indexed by PubMed showed that cancer related genes included SLC25A13, KLHL2, NPC1, WAPL, BARD1, Notch2 and EEF2K. Conclusion Two-directional subtractive cDNA libraries of ALDHhigh and ALDHlow cells were successfully constructed.%目的 构建舌鳞癌Tca8113细胞系中高、低醛脱氢酶活性(high/low aldehyde dehydrogenase activity,ALDHhigh/ALDHlow)细胞差异表达基因cDNA文库.方法 用流式细胞仪检测ALDEFLUOR(R)染色的Tca8113细胞中干细胞标志物ALDH的表达,并收集ALDHhigh和ALDHlow细胞;用Trizol分别提取两亚群细胞的总RNA;用抑制性消减杂交(SSH)对2组RNA进行差异基因筛选和扩增,扩增产物与pMD18-T载体

  3. 促红细胞生成素对大鼠脊髓运动神经元缺氧性损伤的保护作用%Protective Effect of Erythropoietin on Anoxia of Motoneurons after Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    胡杨; 秦文; 廉凯

    2014-01-01

    Objective To observe the protective effect of erythropoietin (EPO) on anoxia of motoneurons after spinal cord injury in rats. Methods The motoneuron was dissociated from neonate Wistar rats and cultivated in vitro with deprivation of oxygen in the medium. The changes of morphology were observed by phase-contrast microscopy, and the expression of EPO receptor (EPOR) was detected with West-ern blotting. The survival rate of motoneuron was measured with methyl thiazolyl tetrazolium (MTT) assay, and the level of lactate dehydro-genase (LDH) was observed. Results Compared with the control group, the expression of EPOR and the level of LDH increased (P<0.01), and the survival rate of motoneuron decreased (P<0.01) in the anoxia group. Compared with the anoxia group, the expression of EPOR and the level of LDH decreased (P<0.05), and the survival rate of motoneuron increased (P<0.01) in the EPO group, which was related with the level of EPO. Conclusion EPO could relieve the damage of motoneuron caused by anoxia, especially by upregulating EPOR.%目的:观察重组红细胞生成素(EPO)对大鼠脊髓运动神经元细胞缺氧性损伤的保护作用。方法对Wistar乳鼠脊髓运动神经元细胞进行原代分离培养,通过去除培养液中氧气来模拟脊髓缺氧。倒置显微镜下观察细胞形态变化,Western blotting检测EPO受体(EPOR)蛋白的表达,噻唑蓝(MTT)比色法及乳酸盐脱氢酶(LDH)活力测定观察加入不同浓度EPO对神经元细胞的保护作用。结果与正常对照组比较,缺氧组脊髓运动神经元缺氧后EPOR表达及LDH浓度明显增加(P<0.01),细胞存活率明显降低(P<0.01);与缺氧组比较, EPO组EPOR表达及LDH浓度降低(P<0.05),细胞存活率明显增强(P<0.01),且与浓度相关。结论EPO可减轻缺氧对运动神经元的损害,而EPOR表达上调可能是EPO发挥其对缺氧神经元保护作用的重要途径之一。

  4. Evaluation of storage performance of special plastic blood bags for apheresis platelets%血小板保存专用塑料血袋的储存性能评价

    Institute of Scientific and Technical Information of China (English)

    王捷熙; 韩颖; 周倩; 刘敏霞; 王艳; 柴丽娜; 卓海龙; 易晓阳; 周建伟; 王建卫

    2015-01-01

    Objective To evaluate the storage performance of storage bags for apheresis platelets produced by Shandong Weigao Group Medical Polymer Co .,Ltd ( experimental bags ) with Trima set platelet storage bags produced by the U .S. Gambro BCT as the control .Method One unit of apheresis platelets was divided into two equal parts , added to control blood bags and experimental blood bags respectively .All samples were stored at ( 22 ±2 )℃ with consecutive oscillation . The platelets′count, mean volume, aggregate activity (ADP, THR), pH, glucose, lactate concentration, lactate dehydro-genase concentration , hypotonic shock reaction , expression of CD62P and phosphatidyl serine on surface of cell membrane were detected at 0,3,5 and 7 d respectively.Results There was no significant difference in platelet quality after five days of storage between the experimental group and the control group (t-test, P>0.05).Conclusion Two types of platelet stor-age blood bags have similar storage performance for apheresis platelets .%目的:以美国Gambro BCT公司生产的Trima set血小板保存袋为对照,评价山东威高集团医用高分子制品股份有限公司生产的血小板保存袋对单采血小板的储存性能。方法将1U单采血小板平分成两份,分别加入实验血袋和对照血袋中,于血小板恒温振荡保存箱中保存。分别于保存0、3、5、7d取样,比较分析两组的血小板含量和血小板平均体积、pH值、体外聚集活性、氧分压和二氧化碳分压、葡萄糖、乳酸和乳酸脱氢酶浓度、低渗休克反应、血小板活化和凋亡、血小板形态结构及细菌培养试验。结果两种保存袋保存的血小板在保存期内,相同保存时间实验组与对照组之间各项检测结果差异无统计学意义(P>0.05);无菌试验均为阴性。结论国产血小板专用塑料血袋与美国Trima set血小板保存袋对该实验使用的15份单采血小板具有相似的储存性能。

  5. Proteomic analysis on differential protein expressions in VSMCs treated with atenolol enantiomers%双向电泳结合MDLC-MS/MS法分析阿替洛尔对映异构体作用后的血管平滑肌细胞差异表达蛋白

    Institute of Scientific and Technical Information of China (English)

    邱峰; 郑姣妮; 邱宗荫

    2011-01-01

    Objective Chiral medicines selectively interact with biological macromolecules through strict chiral recognition and demonstrate different pharmacokinetic characteristics and drug effects. To investi gate the differential protein expressions in vascular smooth muscle cells (VSMCs) treated with 2 atenolol enanti omers, (R) -ATN and (S) -ATN. Methods Cell proliferation was detected with MTT assay when VSMCs were treated with (R)-ATN or (S)-ATN at 0, 0.15, 1.5, 15, 30, 60, 120, 180 and 240 μmol/L respectively for 4 h. After the VSMCs were treated with 120 μmol/L (R)-ATN or (S)-ATN for 4 h, the cell proteins were extracted. Then, differential protein expression was assessed. The differential expression protein spots from (R)/(S)-ATN treated VSMCs were screened by 2-DE, and then analyzed by on-line two-dimensional nano liquid chromatography (HPLC-CHIP included an enrichment column of Zorbax 300SB-C18 and an analytical column of Zorbax 300SB C18 ) coupled with linear ion trap mass spectrometry. Results There were 6 differen tial proteins founded between VSMCs treated by (R)/(S)-ATN, including enhancer of filamentation 1, AP-3 complex subunit beta-l, malate dehydrogenase, mitochondrial precursor, glyceraldehyde-3-phosphate dehydro genase, and uncharacterized protein C3orfl9 were screened. The former 5 proteins were related to cardiovascular events. Conclusion Our results indicates that there are differential protein expressions in VSMCs treated with 2 atenolol enantiomers, (R)-ATN and (S)-ATN, so more attention should be paid chiral drugs.%目的 以双向电泳结合多维色谱串联质谱策略,分析阿替洛尔对映异构体[(R)/(S)-ATN]作用于血管平滑肌细胞(vascular smooth muscle cells, VSMCs)后的差异表达蛋白质.方法 以(R)/(S)-ATN分别作用于VSMCs,提取总蛋白质,双向电泳分离差异表达蛋白点,二维纳流液相色谱芯片(HPLC-CHIP,包含一支纳升级Zorbax 300SB-C18富集柱和一支纳升级Zorbax 300SB-C18分析柱)富

  6. Anestesia em paciente portador de deficiência de glicose-6-fosfato-desidrogenase: relato de caso Anestesia en paciente portador de deficiencia de glicosa-6-fosfato-desidrogenasa: relato de caso Anesthesia in glucose 6-phosphate dehydrogenase-deficient patient: case report

    Directory of Open Access Journals (Sweden)

    Múcio Paranhos de Abreu

    2002-11-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A Deficiência de Glicose-6-Fosfato-Desidrogenase (G6PD é uma enzimopatia relativamente comum, mas as publicações relacionando essa condição com a anestesia são escassas. O objetivo deste relato é apresentar um caso de paciente portador de Deficiência de G6PD, submetido à tenotomia para alongamento de tendão de Aquiles, sob anestesia venosa associada à bloqueio subaracnóideo. Relato do caso: Paciente masculino, 9 anos, 48 kg, portador de deficiência de G6PD e polineuropatia periférica, submetido à tenotomia de tendão de Aquiles, sob anestesia geral venosa com midazolam, propofol e fentanil , associada à bloqueio subaracnóideo com bupivacaína hiperbárica a 0,5%. Ao final da cirurgia o paciente despertou tranqüilo, sem dor ou outras queixas, evoluiu bem, recebendo alta hospitalar sem intercorrências. CONCLUSÕES: Pela evolução do caso relatado, a anestesia subaracnóidea com bupivacaína associada à anestesia venosa total com propofol, mostrou ser uma técnica segura em pacientes portador de deficiência de G6PD.JUSTIFICATIVA Y OBJETIVOS: - La Deficiencia de Glucosa-6-Fosfato-Desidrogenasa (G6PD es una enzimopatia relativamente común, más las publicaciones relacionando esa condición con la anestesia son escasas. El objetivo de este relato es presentar un caso de un paciente portador de Deficiencia de G6PD, sometido a tenotomia para alongamiento de tendón de Aquiles, bajo anestesia venosa asociada al bloqueo subaracnóideo. RELATO DEL CASO: Paciente masculino, 9 años, 48 kg, portador de deficiencia de G6PD y polineuropatia periférica, sometido a tenotomia de tendón de Aquiles, bajo anestesia general venosa con midazolam, propofol y fentanil asociada a bloqueo subaracnóideo con bupivacaína hiperbárica a 0,5%. Al final de la cirugía el paciente despertó tranquilo, sin dolor u otras quejas, evoluyó bien, recibiendo alta hospitalar sin interocurrencias. CONCLUSIONES: Por la evolución del

  7. Erythrocyte glucose-6-phosphate dehydrogenase deficiency in male newborn babies and its relationship with neonatal jaundice Deficiência de glicose-6-fosfato desidrogenase eritrocitária em recém-nascidos do sexo masculino e sua relação com a icterícia neonatal

    Directory of Open Access Journals (Sweden)

    Marli Auxiliadora C. Iglessias

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency, the commonest red cell enzymopathy in humans, has an X-linked inheritance. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic nonspherocytic hemolytic anemia. The incidence of neonatal hyperbilirubinemia is much greater in G6PD-deficient neonates than babies without this deficiency. The aim of this study was to ascertain the presence of neonatal jaundice in erythrocyte G6PD-deficient male newborns. Samples of umbilical cord blood from a total of 204 male newborns of the Januário Cicco School Maternity located in Natal, Rio Grande do Norte, Brazil were analyzed. The G6PD deficiency was identified by the methemoglobin reduction test (Brewer's test. The deficiency was confirmed by quantitative spectrophotometric assay for enzyme activity and cellulose acetate electrophoresis was used to identify the G6PD variant. Eight newborns were found to be G6PD deficient with four of them exhibiting jaundice during the first 48 hours after birth with bilirubin levels higher than 10 mg/dL. All deficient individuals presented the G6PD A- variant at electrophoresis. Our findings confirmed the association between G6PD deficiency and neonatal jaundice. Hence, early diagnosis of the deficiency at birth is essential to control the appearance of jaundice and to prevent the exposure of these newborns to known hemolytic agents.A deficiência de glicose-6-fosfato desidrogenase (G6PD é a anormalidade enzimática hereditária mais frequente. É transmitida como caráter recessivo ligado ao cromossomo X e as principais manifestações clínicas são hemólise induzida por fármacos, icterícia neonatal e anemia hemolítica não esferocítica. O objetivo do estudo foi determinar a presença de icterícia neonatal em recém-nascidos do sexo masculino deficientes de glicose-6-fosfato desidrogenase. Foram analisadas 204 amostras de sangue umbilical de recém-nascidos do sexo

  8. Hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness.

    Science.gov (United States)

    Wu, L Z; Zeng, L H; Ma, Q Y; Xie, Y J; Chen, Y Z; Wu, D Z

    1988-01-01

    The hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness (CCB) were studied. We propose that there is a linkage between the two loci on the X-chromosome determining CCB and glucose-6-phosphate dehydrogenase (G6PD), based on our study of a high incidence of G6PD deficiency in 156 male cases with CCB. The CCB gene is closely linked with that of G6PD deficiency from our pedigree investigations. The rise in the frequency of eight or more whorls, the low value of atd angle and the presenting rate of real palmar patterns of the thenar, hypothenar and I, areas presented the hereditary traits of congenital color blindness.

  9. Selection of Ovine Oocytes by Brilliant Cresyl Blue Staining

    Directory of Open Access Journals (Sweden)

    Liqin Wang

    2012-01-01

    Full Text Available Sheep oocytes derived from the ovaries collected from the slaughterhouse are often used for research on in vitro embryo production, animal cloning, transgenesis, embryonic stem cells, and other embryo biotechnology aspects. Improving the in vitro culture efficiency of oocytes can provide more materials for similar studies. Generally, determination of oocyte quality is mostly based on the layers of cumulus cells and cytoplasm or cytoplasm uniformity and colors. This requires considerable experience to better identify oocyte quality because of the intense subjectivity involved (Gordon (2003, Madison et al. (1992 and De Loos et al. (1992. BCB staining is a function of glucose-6-phosphate dehydrogenase (G6PD activity, an enzyme synthesized in developing oocytes, which decreases in activity with maturation. Therefore, unstained oocytes (BCB− are high in G6PD activity, while the less mature oocytes stains are deep blue (BCB+ due to insuffcient G6PD activity to decolorize the BCB dye.

  10. GLUCOSE -6- PHOSPHATE DEHYDROGENASE DEFICIENCY AND HAEMOGLOBINOPHATIES IN RESIDENT OF ARSO PIR, IRIAN JAYA

    Directory of Open Access Journals (Sweden)

    Trevor R. Jones

    2012-09-01

    Full Text Available Telah dilakukan penelitian tentang defisiensi glukose —6- fosfatase dehidrogenase G-6-PD dan haemoglobinopati dengan populasi 223 penduduk yang terdiri atas 102 suku Jawa dan 121 suku Irian Jaya. Enam orang dari Suku Irian Jaya, ditemukan dengan defisiensi tingkat G-6-PD. Tingkat G-6-PD pada orang-orang ini berkisar antara 4 sampai 50% dari nilai nominal minimum. Ditemukan pula 5 kasus haemoglobinopati. Pada satu orang dari suku Irian Jaya ditemukan haemoglobinopati yang konsisten dengan hemoblobin Lepore-Hollandia. Tiga orang dari suku Jawa menunjukkan suatu varian hemoglobin E dan seorang dari suku Jawa lainnya menunjukkan satu varian yang konsisten dengan hemoglobin fetal. Sementara penemuan ini menunjukkan adanya varian hematologi dalam populasi penelitian yang mungkin berperan dalam kerentanan terhadap malaria, tetapi persentase subyek dengan varian tidak cukup besar untuk mempengaruhi secara berarti angka transmisi malaria di dalam populasi.

  11. Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots

    Directory of Open Access Journals (Sweden)

    Landry Losi

    2010-08-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase deficiency poses a significant impediment to primaquine use for the elimination of liver stage infection with Plasmodium vivax and for gametocyte clearance, because of the risk of life-threatening haemolytic anaemia that can occur in G6PD deficient patients. Although a range of methods for screening G6PD deficiency have been described, almost all require skilled personnel, expensive laboratory equipment, freshly collected blood, and are time consuming; factors that render them unsuitable for mass-screening purposes. Methods A published WST8/1-methoxy PMS method was adapted to assay G6PD activity in a 96-well format using dried blood spots, and used it to undertake population screening within a malaria survey undertaken in Isabel Province, Solomon Islands. The assay results were compared to a biochemical test and a recently marketed rapid diagnostic test. Results Comparative testing with biochemical and rapid diagnostic test indicated that results obtained by filter paper assay were accurate providing that blood spots were assayed within 5 days when stored at ambient temperature and 10 days when stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined by enzyme activity Conclusions The assay enabled simple and quick semi-quantitative population screening in a malaria-endemic region. The study indicated a high prevalence of G6PD deficiency in Isabel Province and highlights the critical need to consider G6PD deficiency in the context of P. vivax malaria elimination strategies in Solomon Islands, particularly in light of the potential role of primaquine mass drug administration.

  12. Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells.

    Science.gov (United States)

    Sun, Y; Gu, X; Zhang, E; Park, M-A; Pereira, A M; Wang, S; Morrison, T; Li, C; Blenis, J; Gerbaudo, V H; Henske, E P; Yu, J J

    2014-05-15

    Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms.

  13. Flaxseed Protects Against Diabetes-Induced Glucotoxicity by Modulating Pentose Phosphate Pathway and Glutathione-Dependent Enzyme Activities in Rats.

    Science.gov (United States)

    Gök, Müslüm; Ulusu, Nuray N; Tarhan, Nilay; Tufan, Can; Ozansoy, Gülgün; Arı, Nuray; Karasu, Çimen

    2016-01-01

    This study investigated the effects of flaxseed (Linum usitatissimum L.) intake on general metabolism, pentose phosphate pathway (PPP) and glutathione-dependent enzymes in diabetic rats. Diabetes was induced by streptozotocin injection (40 mg/kg, i.p.) and the enzyme activities were determined spectrophotometrically. Diabetic and control rats were divided in two subgroups, one untreated, and one treated with flaxseed (0.714 g/kg body weight/day; orally) for 12 weeks. Flaxseed ameliorated decreased body weight (p < .05) and increased blood glucose (p < .001), triglyceride (p < .001), ALT (p < .001) and AST (p < .001) in diabetic rats. Diabetes resulted in increased glucose-6-phosphate dehydrogenase (G6PD) (p < .05) and decreased glutathione-S-transferase (GST) (p < .01), but unchanged 6-phosphogluconate dehydrogenase (6PGD) and glutathione reductase (GR) in the brain of rats. These alterations were partially improved by flaxseed in comparison to diabetic untreated group (p < .05). G6PD, 6PGD, GR were elevated (p < .001), while GST unchanged in the lung of diabetic untreated group compared to control. Flaxseed partially prevented the increase in 6PGD (p < .05) and GR (p < .01), but unaffected G6PD in the lung of diabetic rats. G6PD (p < .001), 6PGD (p < .05), GR (p < .001) were augmented, while GST showed a significant (p < .001) depletion in the pancreas of diabetic untreated rats compared to control. Diabetic alterations observed in pancreatic enzyme activities were significantly prevented by flaxseed. Furthermore, a remarkable decrease in 6PGD (p < .001) and an increase in G6PD (threefold of control) were found in the lens of diabetic untreated group that were completely prevented by flaxseed (p < .001). Flaxseed has beneficial effects against diabetes-induced glucotoxicity by modulating G6PD, 6PGD, GR and GST activities in tissues.

  14. Henna: a potential cause of oxidative hemolysis and neonatal hyperbilirubinemia.

    Science.gov (United States)

    Zinkham, W H; Oski, F A

    1996-05-01

    To evaluate the in vitro oxidation potential of lawsone (2-hydroxy-1,4 naphthoquinone). Lawsone is a chemical present in henna, the crushed leaves of which are used worldwide as a cosmetic agent to stain the hair, skin, and nails. Venous blood from glucose-6-phosphate dehydrogenase (G6PD)-normal and G6PD A- subjects were incubated with various amounts of lawsone for 2 hours at 37 degrees C. Reduced glutathione and methemoglobin (MHb) levels were measured before and after incubation. Final molar concentrations of lawsone in normal blood of 1.4, 2.8, 5.7, and 8.6 x 10-3 mol/L increased MHb percentages from 0.5% to 2.2%, 8.3%, 9.5% and 12.5%, respectively. In a C6PD A- blood, MHb percentages were 19.8%, 32.2%, 44.9%, and 53.9%. At a lawsone concentration of 2.8 x 10-3 mol/L, blood from 15 healthy adults formed MHb percentages of 7.4% +/- 3.3% (+/- 1 SD); in blood from 4 G6PD A- adults, percentages were 44.5%, 40.6%, 41.3%, and 42.8%. Simultaneous measurements of reduced glutathione revealed preincubation values of greater than 40 mg/100 mL of red cells in blood of healthy and G6PD A- subjects. Postincubation values were greater than 40 in blood of healthy subjects and less than 40 in blood of G6PD A- subjects. These in vitro observations indicate that lawsone is an agent capable of causing oxidative hemolysis. In regions of the world where there is a high incidence of G6PD deficiency and unexplained hyperbilirubinemia, oxidative hemolysis secondary to the cutaneous application of henna could be the initiating event.

  15. The effects of chemical and radioactive properties of Tl-201 on human erythrocyte glucose 6-phosphate dehydrogenase activity.

    Science.gov (United States)

    Sahin, Ali; Senturk, Murat; Ciftci, Mehmet; Varoglu, Erhan; Kufrevioglu, Omer Irfan

    2010-04-01

    The inhibitory effects of thallium-201 ((201)Tl) solution on human erythrocyte glucose 6-phosphate dehydrogenase (G6PD) activity were investigated. For this purpose, erythrocyte G6PD was initially purified 835-fold at a yield of 41.7% using 2',5'-Adenosine diphosphate sepharose 4B affinity gel chromatography. The purification was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which showed a single band for the final enzyme preparation. The in vitro and in vivo effects of the (201)Tl solution including Tl(+), Fe(+3) and Cu(+2) metals and the in vitro effects of the radiation effect of the (201)Tl solution and non-radioactive Tl(+), Fe(+3) and Cu(+2) metals on human erythrocyte G6PD enzyme were studied. Enzyme activity was determined with the Beutler method at 340 nm using a spectrophotometer. All purification procedures were carried out at +4 degrees C. (201)Tl solution and radiation exposure had inhibitory effects on the enzyme activity. IC(50) value of (201)Tl solution was 36.86 microl ([Tl(+)]: 0.0036 microM, [Cu(+2)]: 0.0116 microM, [Fe(+3)]: 0.0132 microM), of human erythrocytes G6PD. Seven human patients were also used for in vivo studies of (201)Tl solution. Furthermore, non-radioactive Tl(+), Fe(+3) and Cu(+2) were found not to have influenced the enzyme in vitro. Human erythrocyte G6PD activity was inhibited by exposure for up to 10 minutes to 0.057 mCi/kg (201)Tl solution. It was detected in in vitro and in vivo studies that the human erythrocyte G6PD enzyme is inhibited due to the radiation effect of (201)Tl solution. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Platelet enzyme abnormalities in leukemias

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    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  17. Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle cell trait among blood donors in Riyadh

    Directory of Open Access Journals (Sweden)

    Alabdulaali Mohammed

    2010-01-01

    Full Text Available Background and Aims: Blood donation from glucose-6-phosphate dehydrogenase (G6PD-deficient and sickle cell trait (SCT donors might alter the quality of the donated blood during processing, storage or in the recipient′s circulatory system. The aim of this study was to determine the prevalence of G6PD deficiency and SCT among blood donors coming to King Khalid University Hospital (KKUH in Riyadh. It was also reviewed the benefits and risks of transfusing blood from these blood donors. Materials and Methods: This cross-sectional study was conducted on 1150 blood samples obtained from blood donors that presented to KKUH blood bank during the period April 2006 to May 2006. All samples were tested for Hb-S by solubility test, alkaline gel electrophoresis; and for G6PD deficiency, by fluorescent spot test. Results: Out of the 1150 donors, 23 (2% were diagnosed for SCT, 9 (0.78% for G6PD deficiency and 4 (0.35% for both conditions. Our prevalence of SCT and G6PD deficiency is higher than that of the general population of Riyadh. Conclusion: We recommend to screen all units for G6PD deficiency and sickle cell trait and to defer donations from donors with either of these conditions, unless if needed for special blood group compatibility, platelet apheresis or if these are likely to affect the blood bank inventory. If such blood is to be used, special precautions need to be undertaken to avoid complications in high-risk recipients.

  18. Improved localization of glucose-6-phosphate dehydrogenase activity in cells with 5-cyano-2,3-ditolyl-tetrazolium chloride as fluorescent redox dye reveals its cell cycle-dependent regulation.

    Science.gov (United States)

    Frederiks, Wilma M; van Marle, Jan; van Oven, Carel; Comin-Anduix, Begonya; Cascante, Marta

    2006-01-01

    Since the introduction of cyano-ditolyl-tetrazolium chloride (CTC), a tetrazolium salt that gives rise to a fluorescent formazan after reduction, it has been applied to quantify activity of dehydrogenases in individual cells using flow cytometry. Confocal laser scanning microscopy (CLSM) showed that the fluorescent formazan was exclusively localized at the surface of individual cells and not at intracellular sites of enzyme activity. In the present study, the technique has been optimized to localize activity of glucose-6-phosphate dehydrogenase (G6PD) intracellularly in individual cells. Activity was demonstrated in cultured fibrosarcoma cells in different stages of the cell cycle. Cells were incubated for the detection of G6PD activity using a medium containing 6% (w/v) polyvinyl alcohol, 5 mM CTC, magnesium chloride, sodium azide, the electron carrier methoxyphenazine methosulphate, NADP, and glucose-6-phosphate. Before incubation, cells were permeabilized with 0.025% glutaraldehyde. Fluorescent formazan was localized exclusively in the cytoplasm of fibrosarcoma cells. The amount of fluorescent formazan in cells increased linearly with incubation time when measured with flow cytometry and CLSM. When combining the Hoechst staining for DNA with the CTC method for the demonstration of G6PD activity, flow cytometry showed that G6PD activity of cells in S phase and G2/M phase is 27 +/- 4% and 43 +/- 4% higher, respectively, than that of cells in G1 phase. CLSM revealed that cells in all phases of mitosis as well as during apoptosis contained considerably lower G6PD activity than cells in interphase. It is concluded that posttranslational regulation of G6PD is responsible for this cell cycle-dependent activity.

  19. Purification and Characterization of Glucose-6-Phosphate Dehydrogenase from Camel Liver

    Directory of Open Access Journals (Sweden)

    Mahmoud A. Ibrahim

    2014-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase from camel liver was purified to homogeneity by ammonium sulfate precipitation and a combination of DEAE-cellulose, Sephacryl S-300 gel filtration, and 2′, 5′ ADP Sepharose 4B affinity chromatography columns. The specific activity of camel liver G6PD is increased to 1.80438 units/mg proteins with 63-fold purification. It turned out to be homogenous on both native PAGE and 12% SDS PAGE, with a molecular weight of 64 kDa. The molecular weight of the native form of camel liver G6PD was determined to be 194 kDa by gel filtration indicating a trimeric protein. The Km value was found to be 0.081 mM of NADP+. Camel liver G6PD displayed its optimum activity at pH 7.8 with an isoelectric point (pI of pH 6.6–6.8. The divalent cations MgCl2, MnCl2, and CoCl2 act as activators; on the other hand, CaCl2 and NiCl2 act as moderate inhibitors, while FeCl2, CuCl2, and ZnCl2 are potent inhibitors of camel liver G6PD activity. NADPH inhibited camel liver G6PD competitively with Ki value of 0.035 mM. One binding site was deduced for NADPH on the enzyme molecule. This study presents a simple and reproducible purification procedure of G6PD from the camel liver.

  20. Dicty_cDB: SFI140 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available EQCHN59 Gallus gallus cDNA clone ChEST370a22 5', mRNA sequence. 42 0.28 2 BG711333 | ( S74728 ) antiquitin=26g turgor...genase family 7 member A1... 110 3e-23 AY883858_1( AY883858 |pid:none) Sterkiella histriomuscorum turgor

  1. InterProScan Result: BY940643 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available GENASE 3.4e-53 T IPR005708 Homogentisate 1,2-dioxygenase Biological Process: L-phenylalanine catabolic proce...ss (GO:0006559)|Biological Process: tyrosine metabolic process (GO:0006570)|Biological Process: oxidation reduction (GO:0055114) ...

  2. InterProScan Result: FS863249 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available GENASE 1.3e-139 T IPR005708 Homogentisate 1,2-dioxygenase Biological Process: L-phenylalanine catabolic proc...ess (GO:0006559)|Biological Process: tyrosine metabolic process (GO:0006570)|Biological Process: oxidation reduction (GO:0055114) ...

  3. Glucose-6-Phosphate Dehydrogenase Deficiency and Adrenal Hemorrhage in a Filipino Neonate with Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Akira Ohishi

    2013-05-01

    Full Text Available We report on a Filipino neonate with early onset and prolonged hyperbilirubinemia who was delivered by a vacuum extraction due to a prolonged labor. Subsequent studies revealed adrenal hemorrhage and glucose-6-phosphate dehydrogenase (G6PD deficiency. It is likely that asphyxia and resultant hypoxia underlie the occurrence of adrenal hemorrhage and the clinical manifestation of G6PD deficiency and that the presence of the two events explains the early onset and prolonged hyperbilirubinemia of this neonate. Our results represent the importance of examining possible underlying factors for the development of severe, early onset, or prolonged hyperbilirubinemia.

  4. Effect ofVitex negundo leaf extract on the free radicals scavengers in complete Freund's adjuvant induced arthritic rats

    OpenAIRE

    Devi, P. Renuka; Kumari, S Krishna; Kokilavani, C

    2007-01-01

    The effect of the oral administration ofVitex negundo leaf extract on the levels of enzymic and non-enzymic antioxidants were studied in the adjuvant induced arthritic (AIA) rats The levels of antioxidant enzymes such as SOD, CAT, GPx, G6PD, GSH and Vit-C were estimated in various groups of the experimental rats. It was observed that the antioxidant enzyme levels in the AIA were significantly low when compared to normal rats. A significant decrease in enzymic antioxidant—SOD, CAT, GPx, G6PD a...

  5. Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated mechanism and its role in prostate cancer cell growth.

    Science.gov (United States)

    Tsouko, E; Khan, A S; White, M A; Han, J J; Shi, Y; Merchant, F A; Sharpe, M A; Xin, L; Frigo, D E

    2014-05-26

    Cancer cells display an increased demand for glucose. Therefore, identifying the specific aspects of glucose metabolism that are involved in the pathogenesis of cancer may uncover novel therapeutic nodes. Recently, there has been a renewed interest in the role of the pentose phosphate pathway in cancer. This metabolic pathway is advantageous for rapidly growing cells because it provides nucleotide precursors and helps regenerate the reducing agent NADPH, which can contribute to reactive oxygen species (ROS) scavenging. Correspondingly, clinical data suggest glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, is upregulated in prostate cancer. We hypothesized that androgen receptor (AR) signaling, which plays an essential role in the disease, mediated prostate cancer cell growth in part by increasing flux through the pentose phosphate pathway. Here, we determined that G6PD, NADPH and ribose synthesis were all increased by AR signaling. Further, this process was necessary to modulate ROS levels. Pharmacological or molecular inhibition of G6PD abolished these effects and blocked androgen-mediated cell growth. Mechanistically, regulation of G6PD via AR in both hormone-sensitive and castration-resistant models of prostate cancer was abolished following rapamycin treatment, indicating that AR increased flux through the pentose phosphate pathway by the mammalian target of rapamycin (mTOR)-mediated upregulation of G6PD. Accordingly, in two separate mouse models of Pten deletion/elevated mTOR signaling, Pb-Cre;Pten(f/f) and K8-CreER(T2);Pten(f/f), G6PD levels correlated with prostate cancer progression in vivo. Importantly, G6PD levels remained high during progression to castration-resistant prostate cancer. Taken together, our data suggest that AR signaling can promote prostate cancer through the upregulation of G6PD and therefore, the flux of sugars through the pentose phosphate pathway. Hence, these findings support a

  6. INCIDENCE OF ERYTHROCYTE GLUCOSE-6-PHOSPHATE- DEHYDROGENASE DEFICIENCY

    Directory of Open Access Journals (Sweden)

    Sh. Rahbar

    1974-06-01

    The fluorescent spot technique was used for screening and qualitative determination of G-6-PD in erythrocytes. This technique was compared with other methods of G-6-PD enzyme assay and proved to be very reliable. Qualitative enzyme estimation was carried out with spectrophotometer methods. A total of 738 specimens tested and some degree of enzyme deficiencies were detected. In 20 specimens there was a complete enzyme deficiency and in 5 cases the enzyme activity was between 15 to 50 percent of normal subject. The data suggests, the blood bank should be warned of transfusion of enzyme deficient bloods to the patients with fauvism.

  7. Deficiencia de glucosa-6-fosfato deshidrogenasa: De lo clínico a lo bioquímico

    OpenAIRE

    Saúl Gómez-Manzo; Gabriel López-Velázquez; Itzhel García-Torres; Gloria Hernández-Alcantara; Sara Teresa Méndez-Cruz; Jaime Marcial-Quino; Adriana Castillo-Villanueva; Sergio Enríquez-Flores; Ignacio De la Mora; Angélica Torres-Arroyo; Horacio Reyes-Vivas; Jesús Oria-Hernández

    2014-01-01

    La deficiencia de Glucosa-6-fosfato deshidrogenasa (G6PD) es la enzimopatía más frecuente, con una prevalencia global del 4,9% y con alrededor de 330 a 400 millones de personas afectadas en el mundo. La G6PD desempeña un papel fundamental en el equilibrio redox intracelular, especialmente en los eritrocitos; en condiciones de estrés oxidativo inducido (por ejemplo, por exposición a agentes externos como fármacos, alimentos o infecciones), los hematíes portadores de la variante enzimática y...

  8. Malaria, favism and glucose-6-phosphate dehydrogenase deficiency.

    Science.gov (United States)

    Huheey, J E; Martin, D L

    1975-10-15

    Although glucose-6-phosphate dehydrogenase deficient individuals may suffer (sometimes fatally) from favism, a high incidence of this trait occurs in many Mediterranean populations. This apparent paradox is explained on the basis of a synergistic interaction between favism and G-6-PD deficiency that provides increased protection against malaria compared to that of the G-6-PD deficiency alone. This relationship is analogous to that between various hemoglobins and malaria in that there is selection for a more severe trait if it provides more protection against malaria.

  9. Risks of hemolysis in glucose-6-phosphate dehydrogenase deficient infants exposed to chlorproguanil-dapsone, mefloquine and sulfadoxine-pyrimethamine as part of intermittent presumptive treatment of malaria in infants

    DEFF Research Database (Denmark)

    Poirot, Eugenie; Vittinghoff, Eric; Ishengoma, Deus;

    2015-01-01

    BACKGROUND: Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimala......BACKGROUND: Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi...

  10. SwissProt search result: AK121655 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121655 J033061N09 (P23522) 2-dehydro-3-deoxyglucarate aldolase (EC 4.1.2.20) (2-keto-3-deoxyglucar...ate aldolase) (2-dehydro-3-deoxygalactarate aldolase) (DDG aldolase) (5-keto-4-deoxy-D-glucarate aldolase) (KDGlucA) GARL_ECOLI 1e-13 ...

  11. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...

  12. Triiodothyronine (T3)-associated upregulation and downregulation of nuclear T3 binding in the human fibroblast cell (MRC-5)--stimulation of malic enzyme, glucose-6-phosphate-dehydrogenase, and 6-phosphogluconate-dehydrogenase by insulin, but not by T3

    DEFF Research Database (Denmark)

    Matzen, L E; Kristensen, S R; Kvetny, J

    1991-01-01

    The specific nuclear binding of triiodothyronine (T3) (NBT3) and the activity of malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PD), and 6-phosphogluconate-dehydrogenase (6PGD) were studied in the human fibroblast cell (MRC-5). The overall apparent binding affinity (Ka) was 2.7 x 10(9) L...

  13. Clinical Significance of UGT1A1 Genetic Analysis in Chinese Neonates with Severe Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Hui Yang

    2016-08-01

    Conclusion: Besides G6PD-deficiency screening, UGT1A1 genetic analysis, and especially the UGT1A1*6(c.211G>A, p.Arg71Gly polymorphism detection, may be taken into consideration for early diagnosis and treatment of severe hyperbilirubinemic newborns in southern China.

  14. Glucose-6-phosphate dehydrogenase deficiency and reduced haemoglobin levels in African children with severe malaria

    National Research Council Canada - National Science Library

    Nguetse, Christian N; Meyer, Christian G; Adegnika, Ayola Akim; Agbenyega, Tsiri; Ogutu, Bernhards R; Kremsner, Peter G; Velavan, Thirumalaisamy P

    2016-01-01

    .... A total of 301 Gabonese, Ghanaian, and Kenyan children aged 6-120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A(+)) and deficient (type...

  15. Methemoglobinemia

    Science.gov (United States)

    ... check levels of gases in the blood ( arterial blood gas analysis ) Treatment People with hemoglobin M disease don't have symptoms. So, they may not need treatment. A medicine called ... risk for a blood disease called G6PD deficiency . They should not take ...

  16. Multiple independent fusions of glucose-6-phosphate dehydrogenase with enzymes in the pentose phosphate pathway.

    Directory of Open Access Journals (Sweden)

    Nicholas A Stover

    Full Text Available Fusions of the first two enzymes in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD and 6-phosphogluconolactonase (6PGL, have been previously described in two distant clades, chordates and species of the malarial parasite Plasmodium. We have analyzed genome and expressed sequence data from a variety of organisms to identify the origins of these gene fusion events. Based on the orientation of the domains and range of species in which homologs can be found, the fusions appear to have occurred independently, near the base of the metazoan and apicomplexan lineages. Only one of the two metazoan paralogs of G6PD is fused, showing that the fusion occurred after a duplication event, which we have traced back to an ancestor of choanoflagellates and metazoans. The Plasmodium genes are known to contain a functionally important insertion that is not seen in the other apicomplexan fusions, highlighting this as a unique characteristic of this group. Surprisingly, our search revealed two additional fusion events, one that combined 6PGL and G6PD in an ancestor of the protozoan parasites Trichomonas and Giardia, and another fusing G6PD with phosphogluconate dehydrogenase (6PGD in a species of diatoms. This study extends the range of species known to contain fusions in the pentose phosphate pathway to many new medically and economically important organisms.

  17. Aphrodisiac drug-induced hemolysis.

    Science.gov (United States)

    Stalnikowicz, Ruth; Amitai, Yona; Bentur, Yedidia

    2004-01-01

    Volatile alkyl nitrites have been used during the past decades for "recreational purposes," and for intensifying sexual experience. Their use has been associated with methemoglobinemia and hemolysis. We report three patients who presented over the past year with acute hemolysis after inhalation of butyl nitrite, two of them had glucose-6-phosphate dehydrogenase (G6PD) deficiency.

  18. Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia.

    Directory of Open Access Journals (Sweden)

    Samuel Dunyo

    Full Text Available BACKGROUND: Chlorproguanil-dapsone (Lapdap, developed as a low-cost antimalarial, was withdrawn in 2008 after concerns about safety in G6PD deficient patients. This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine (AL under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia. We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure. METHODS: 1238 children aged 6 months to 10 years with uncomplicated malaria were randomized to receive CD or artemether-lumefantrine (AL and followed for 28 days. The first dose was supervised, subsequent doses given unsupervised at home. G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia. The main endpoints were clinical treatment failure by day 28, incidence of severe anaemia (Hb<5 g/dL, and haemoglobin concentration on day 3. FINDINGS: One third of patients treated with AL, and 6% of patients treated with CD, did not complete their course of medication. 18% (109/595 of children treated with CD and 6.1% (36/587 with AL required rescue medication within 4 weeks, risk difference 12% (95%CI 8.9%-16%. 23 children developed severe anaemia (17 (2.9% treated with CD and 6 (1.0% with AL, risk difference 1.8%, 95%CI 0.3%-3.4%, P = 0.02. Haemoglobin concentration on day 3 was lower among children treated with CD than AL (difference 0.43 g/dL, 95% CI 0.24 to 0.62, and within the CD group was lower among those children who had higher parasite density at enrollment. Only 17 out of 1069 children who were typed were G6PD A- deficient, of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia. 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3. INTERPRETATION: AL was well tolerated and highly effective and when

  19. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

    Science.gov (United States)

    Mwaiswelo, Richard; Ngasala, Billy E; Jovel, Irina; Gosling, Roland; Premji, Zul; Poirot, Eugenie; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas

    2016-06-10

    This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart™) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm. Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient

  20. Associations between Red Cell Polymorphisms and Plasmodium falciparum Infection in the Middle Belt of Ghana

    Science.gov (United States)

    Amoako, Nicholas; Asante, Kwaku Poku; Adjei, George; Awandare, Gordon A.; Bimi, Langbong; Owusu-Agyei, Seth

    2014-01-01

    Background Red blood cell (RBC) polymorphisms are common in malaria endemic regions and are known to protect against severe forms of the disease. Therefore, it is important to screen for these polymorphisms in drugs or vaccines efficacy trials. This study was undertaken to evaluate associations between clinical malaria and RBC polymorphisms to assess biological interactions that may be necessary for consideration when designing clinical trials. Method In a cross-sectional study of 341 febrile children less than five years of age, associations between clinical malaria and common RBC polymorphisms including the sickle cell gene and G6PD deficiency was evaluated between November 2008 and June 2009 in the middle belt of Ghana, Kintampo. G6PD deficiency was determined by quantitative methods whiles haemoglobin variants were determined by haemoglobin titan gel electrophoresis. Blood smears were stained with Giemsa and parasite densities were determined microscopically. Results The prevalence of clinical malarial among the enrolled children was 31.9%. The frequency of G6PD deficiency was 19.0% and that for the haemoglobin variants were 74.7%, 14.7%, 9.1%, 0.9% respectively for HbAA, HbAC, HbAS and HbSS. In Multivariate regression analysis, children with the HbAS genotype had 79% lower risk of malaria infection compared to those with the HbAA genotypes (OR = 0.21, 95% CI: 0.06–0.73, p = 0.01). HbAC genotype was not significantly associated with malaria infection relative to the HbAA genotype (OR = 0.70, 95% CI: 0.35–1.42, p = 0.33). G6PD deficient subgroup had a marginally increased risk of malaria infection compared to the G6PD normal subgroup (OR = 1.76, 95% CI: 0.98–3.16, p = 0.06). Conclusion These results confirm previous findings showing a protective effect of sickle cell trait on clinical malaria infection. However, G6PD deficiency was associated with a marginal increase in susceptibility to clinical malaria compared to children without

  1. Pyrrolizidine alkaloids in food: a spectrum of potential health consequences.

    Science.gov (United States)

    Edgar, J A; Colegate, S M; Boppré, M; Molyneux, R J

    2011-03-01

    Contamination of grain with 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs) and their N-oxides is responsible for large incidents of acute and subacute food poisoning, with high morbidity and mortality, in Africa and in central and south Asia. Herbal medicines and teas containing dehydroPAs have also caused fatalities in both developed and developing countries. There is now increasing recognition that some staple and widely consumed foods are sometimes contaminated by dehydroPAs and their N-oxides at levels that, while insufficient to cause acute poisoning, greatly exceed maximum tolerable daily intakes and/or maximum levels determined by a number of independent risk assessment authorities. This suggests that there may have been cases of disease in the past not recognised as resulting from dietary exposure to dehydroPAs. A review of the literature shows that there are a number of reports of liver disease where either exposure to dehydroPAs was suspected but no source was identified or a dehydroPA-aetiology was not considered but the symptoms and pathology suggests their involvement. DehydroPAs also cause progressive, chronic diseases such as cancer and pulmonary arterial hypertension but proof of their involvement in human cases of these chronic diseases, including sources of exposure to dehydroPAs, has generally been lacking. Growing recognition of hazardous levels of dehydroPAs in a range of common foods suggests that physicians and clinicians need to be alert to the possibility that these contaminants may, in some cases, be a possible cause of chronic diseases such as cirrhosis, pulmonary hypertension and cancer in humans.

  2. Immune Thrombocytopenia Resolved by Eltrombopag in a Carrier of Glucose-6-Phosphate Dehydrogenase Deficiency

    Directory of Open Access Journals (Sweden)

    Laura Scaramucci

    2016-03-01

    Full Text Available Eltrombopag, a thrombopoietin mimetic peptide, may provide excellent clinical efficacy in steroid-refractory patients with immune thrombocytopenic purpura (ITP [1,2]. Eltrombopag is generally well tolerated. However, its use in the particular setting of glucose-6-phosphate dehydrogenase (G6PD and history of acute hemolytic anemia (AHA has not been reported so far. A 51-year-old female was diagnosed as having ITP in September 2014. She was not taking any medication and her past history was negative, apart from having been diagnosed a carrier (heterozygous of G6PD deficiency (Mediterranean variant after a familial screening by molecular and biochemical methods. She presented with only slightly reduced (about 50% enzyme level, belonging to World Health Organization-defined class 3 [3,4]. In the following years, the patient experienced some episodes of AHA, which were managed at outside institutions; in particular, a severe episode of AHA, probably triggered by urinary infection and antibiotics [5], had complicated her second and last delivery. The hemolytic episodes were selflimiting and resolved without sequelae. No other causes of hemolysis were documented. When the case came to our attention, a diagnosis of ITP was made; hemolytic parameters were normal, although the G6PD enzyme concentration was not measured. Oral prednisone (1 mg/kg was given with only a transient benefit. The patient was then a candidate for elective splenectomy. However, given her extremely low platelet count, she was started in October 2014 on eltrombopag at 50 mg/day as a bridge to splenectomy. Given that, to the best of our knowledge, the use of this drug has never been reported in the particular setting of G6PD deficiency, the patient was constantly monitored. A prompt platelet increase (178x109/L was observed 1 week after the start of treatment. After she achieved the target platelet count, the dose of eltrombopag was tapered to the lowest effective dose. The patient

  3. Cardiovascular safety of etoricoxib

    Directory of Open Access Journals (Sweden)

    Viktoriya Georgievna Barskova

    2011-01-01

    Full Text Available Meticulous attention is paid to the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs, the so-called selective cyclooxy-genase 2 (COX-2 inhibitors in particular. The author considers precisely this matter in case of Russia's recent NSAID etoricoxib that has been tested along with other most studied medications from this group, by applying one of the latest meta-analyses. The EULAR recommendations to use NSAIDs are given.

  4. Drug: D01547 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 01547.gif Analgesia [DS:H00445 H00630] Therapeutic category: 1149 cyclooxygenase-1 (COX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxy... Target-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase...-1 (COX-1) [HSA:5742] [KO:K00509] Zaltoprofen D01547 Zaltoprofen (JP16/INN) cyclooxygenase-2 (COX-2)...genase-2 (COX-2) inhibitor [HSA:5743] [KO:K11987] hsa00590(5742+5743) Arachidonic a

  5. PPARα, PPARγ and SREBP-1 pathways mediated waterborne iron (Fe)-induced reduction in hepatic lipid deposition of javelin goby Synechogobius hasta.

    Science.gov (United States)

    Chen, Guang-Hui; Luo, Zhi; Chen, Feng; Shi, Xi; Song, Yu-Feng; You, Wen-Jing; Liu, Xu

    2017-07-01

    The 42-day experiment was conducted to investigate the effects and mechanism of waterborne Fe exposure influencing hepatic lipid deposition in Synechogobius hasta. For that purpose, S. hasta were exposed to four Fe concentrations (0 (control), 0.36, 0.72 and 1.07μM Fe) for 42days. On days 21 and 42, morphological parameters, hepatic lipid deposition and Fe contents, and activities and mRNA levels of enzymes and genes related to lipid metabolism, including lipogenic enzymes (6PGD, G6PD, ME, ICDH, FAS and ACC) and lipolytic enzymes (CPTI, HSL), were analyzed. With the increase of Fe concentration, hepatic Fe content tended to increase but HSI and lipid content tended to decrease. On day 21, Fe exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as well as the mRNA levels of G6PD, ACCa, FAS, SREBP-1 and PPARγ, but up-regulated CPT I, HSLa and PPARα mRNA levels. On day 42, Fe exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as well as the mRNA levels of 6PGD, ACCa, FAS and SREBP-1, but up-regulated CPT I, HSLa, PPARα and PPARγ mRNA levels. Using primary S. hasta hepatocytes, specific pathway inhibitors (GW6471 for PPARα and fatostatin for SREBP-1) and activator (troglitazone for PPARγ) were used to explore the signaling pathways of Fe reducing lipid deposition. The GW6471 attenuated the Fe-induced down-regulation of mRNA levels of 6PGD, G6PD, ME, FAS and ACCa, and attenuated the Fe-induced up-regulation of mRNA levels of CPT I, HSLa and PPARα. Compared with single Fe-incubated group, the mRNA levels of G6PD, ME, FAS, ACCa, ACCb and PPARγ were up-regulated while the CPT I mRNA levels were down-regulated after troglitazone pre-treatment; fatostatin pre-treatment down-regulated the mRNA levels of 6PGD, ME, FAS, ACCa, ACCb and SREBP-1, and increased the CPT I and HSLa mRNA levels. Based on these results above, our study indicated that Fe exposure reduced hepatic lipid deposition by down-regulating lipogenesis

  6. An optimised system for refolding of human glucose 6-phosphate dehydrogenase

    Directory of Open Access Journals (Sweden)

    Engel Paul C

    2009-03-01

    Full Text Available Abstract Background Human glucose 6-phosphate dehydrogenase (G6PD, active in both dimer and tetramer forms, is the key entry enzyme in the pentose phosphate pathway (PPP, providing NADPH for biosynthesis and various other purposes, including protection against oxidative stress in erythrocytes. Accordingly haemolytic disease is a major consequence of G6PD deficiency mutations in man, and many severe disease phenotypes are attributed to G6PD folding problems. Therefore, a robust refolding method with high recovery yield and reproducibility is of particular importance to study those clinical mutant enzymes as well as to shed light generally on the refolding process of large multi-domain proteins. Results The effects of different chemical and physical variables on the refolding of human recombinant G6PD have been extensively investigated. L-Arg, NADP+ and DTT are all major positive influences on refolding, and temperature, protein concentration, salt types and other additives also have significant impacts. With the method described here, ~70% enzyme activity could be regained, with good reproducibility, after denaturation with Gdn-HCl, by rapid dilution of the protein, and the refolded enzyme displays kinetic and CD properties indistinguishable from those of the native protein. Refolding under these conditions is relatively slow, taking about 7 days to complete at room temperature even in the presence of cyclophilin A, a peptidylprolyl isomerase reported to increase refolding rates. The refolded protein intermediates shift from dominant monomer to dimer during this process, the gradual emergence of dimer correlating well with the regain of enzyme activity. Conclusion L-Arg is the key player in the refolding of human G6PD, preventing the aggregation of folding intermediate, and NADP+ is essential for the folding intermediate to adopt native structure. The refolding protocol can be applied to produce high recovery yield of folded protein with

  7. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.

    Science.gov (United States)

    Dong, Tieying; Kang, Xinmei; Liu, Zhaoliang; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Liu, Hang; Wang, Zhipeng; Zhang, Qingyuan

    2016-06-01

    Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic

  8. The Specific Expression of Isozymes in Leuciscus merzbacheri Tissues%准噶尔雅罗鱼组织同工酶表达特性

    Institute of Scientific and Technical Information of China (English)

    路李鹏; 董艳艳; 胡文革; 王佳君; 陈登稳; 王孝国

    2012-01-01

    使用不连续PAGE法,分析了10尾准噶尔雅罗鱼(Leuciscus merzbacheri)眼睛、鳃、皮、背部肌肉、鳍和肝胰脏6种组织的10种同工酶(LDH,CCO,EST,CAT,POD,ME,MDH,G6PD,GDH,ADH)的差异表达,并对部分同工酶基因位点及表达酶谱表型进行了分析,以期为其种质资源保护和开发以及遗传育种等方面的研究提供基础资料.结果显示,10种同工酶中9种在6种组织中出现了明显的组织差异性,仅CCO在6种组织中的差异性较小.在对准噶尔雅罗鱼的10种同工酶的遗传多样性分析中,共记录到了21个基因位点,其中Est-1、Me-B、s-MDH、G6pd-A、G6pd-B和Adh-A为多态性基因位点.多态位点比例为:P =6/21=28.57%.%Polyacrylamide gel electrophoresis was used to detect the expression of ten isozymes (LDH, CCO, EST, CAT, POD, ME, MDH, G6PD, GDH, and ADH) in six different tissues, including eye, gill, skin, muscle, fin, and liver. Part of isozymes gene loci and zymograms were analyzed for providing the foundation for conservation and development of germplasm resources and genetic breeding. The results showed that the electrophoresis patterns of isozymes exhibited an apparent tissue-specificity except for CCO which showed no evident difference in 6 tissues examined. Biochemical genetic analysis showed that the ten isozymes were coded by 21 gene loci, six of which were found to be polymorphic. Finally, based on the zymograms, six isozymes including Est-1 , Me-B, s-MDH, G6pd-A, G6pd-B and Adh-A were analyzed genetically for their subunit structure, coding gene loci and numbers as well as their specific expression, and the proportion of polymorphic loci was P= 6/21 =28. 57%.

  9. Clinical analysis of ABO hemolytic disease in newborn with giucose-6-phosphate dehydrogenase deficiency.%新生儿ABO溶血病并红细胞葡萄糖-6-磷酸脱氢酶缺乏症临床对比分析

    Institute of Scientific and Technical Information of China (English)

    黄世荣; 段捷华

    2010-01-01

    目的 探讨新生儿ABO溶血病、红细胞葡萄糖-6-磷酸脱氢酶(G-6-PD)缺乏症及两者合并患儿的临床特点.方法 对160例新生儿ABO溶血病(ABO组)、219例G-6-PD缺乏症(G6PD组)、52例新生儿ABO溶血病并G-6-PD缺乏症(ABO+G617D组)3组临床相关指标进行对比分析.结果 G6PD组血红蛋白[(159.7±24.9)g/L]高于ABO组[(150.2±23.0)g/L]和ABO+G6PD组[(149.2±22.8)g/L],差异均有统计学意义(P均<0.01);血清总胆红紊高于ABO组[(419.0±152.9)μmol/L与(355.4±113.2)μmol/L],差异有统计学意义(P<0.01);黄疸消退时间较ABO组长[(9.4±2.3)d与(8.1±2.2)d],差异有统计学意义(P<0.01).ABO+G6PD组黄疸消退时间[(12.0±2.7)d]、光疗时间[(43.2±16.0)h]、光疗次数[(3.5±1.2)次]均长或多于ABO组[(8.1.4-2.2)d、(36.1 4-15.9)h、(2.6±1.2)次]及其G6PD组[(9.4±2.3)d、(37.6±17.3)h、(2.8 4-1.3)次],差异均有统计学意义(P均<0.05).G6PD组胆红素脑病(16.O%)、低钙血症发生率(32.9%)高于ABO组(6.9%、20.0%),差异有统计学意义(P<0.05);而其贫血发生率(23.3%)则低于ABO组(40.0%)及其ABO+G6PD组(51.9%),差异有统计学意义(P<0.01).结论 新生儿ABO溶血病并G-6-PD缺乏症时,黄疸出现时间、黄疸程度、胆红素脑病发生率与新生儿ABO溶血病、G-6-PD缺乏症差异无显著性,但黄疸消退时间更长,黄疸更易反复.G-6-PD缺乏症与新生儿ABO溶血痛相比,黄疸程度更重,退黄时间更长,更易发生胆红素脑病,但贫血发生率更低.%Objective To explore the clinical features of ABO hemolytic disease in newboms,red blood cell glucose-6-phosphate dehydrogenase(G-6-PD) deficiency and the combined. Methods In the study, 160 cases of ABO hemolytic disease in newborn (ABO group) ,219 cases of G-6-PD deficiency(G6PD group) ,52 cases of the combined(ABO + G6PD group). The three groups were analyzed. Results The hemoglobin in the G6PD group ( (159. 7 ± 24.9) g/L) was significantly higher than in the ABO group ((150. 2

  10. Reference: PREATPRODH [PLACE

    Lifescience Database Archive (English)

    Full Text Available PREATPRODH Satoh R, Nakashima K, Seki M, Shinozaki K, Yamaguchi-Shinozaki K. ACTCAT..., a novel cis-acting element for proline- and hypoosmolarity-responsive expression of the ProDH gene encoding proline dehydro

  11. pyran Derivatives

    African Journals Online (AJOL)

    NICO

    supported ... various organic transformations such as oxidation, dehydro- genation .... precipitate was next washed with distilled water and acetone. The product ... was stirred for 5–10 min before been treated with dimedone. (1 mmol) and ...

  12. 大鼠海马神经元体外氧糖剥夺/复氧模型的构建%The experimental probe into the construction of oxygen glucose deprivation/reoxygenation model of hippocampal neurons of rat in vitro

    Institute of Scientific and Technical Information of China (English)

    姜骏; 符岳; 方向韶; 常建星; 蒋龙元; 黄子通

    2010-01-01

    Objective To establish the oxygen glucose deprivation (OGD)/reoxygenation experimental model of hippocatnpal neurons of rat in vitro, and to try to identify the length of time for producing optimum injury in this model. Method The primary hippocampal neurons of newborn Sprague-Dawley rats were cultured for 7 days and randomly (random number) divided into a control group and OGD groups. The OGD groups were assigned into 1 h, 2 h, 4 h, 6h, 8 h and 10 h subgroups in accordance with different lengths of time for oxygen glucose deprivation. The neurons of OGD groups were placed into a tri-gas incubator containing 0.5% oxygen and the culture medium was substituted with the glucose-free Earle' s balanced salt solution, simulating cerebral ischemia injury in vivo. The morphology of neurons was observed after reoxygenation for 24 hours. The MIT assay was used to determine the rate of survived cells derived from the value of optical density (OD) of cells. The lactate dehydro-genase (LDH) content in culture medium was detected to evaluate the neuron injury. The apoptotic rate of neurons was measured by using flow cytometry. Dunnett-test and Spearman correlation analysis were used to analyze the data with SPSS version 16.0 soft ware package. Results The morphological damage of neurons in OGD groups aggravated gradually, optical density and cell survival rate decreased (rs= -0.961 and rs = -0.966, P <0.01), and the amount of LDH increased (rs = 0.990, P <0.01) with longer duration of exposure to oxygen glucose deprivation, and the rate of neuron apoptosis increased obviously which was significantly statistical difference in com-parison with the control group (P < 0.05). Under the setting of oxygen glucose deprivation for 6 hours, the apop-tosis rate of neurons approximated to 50% . Conclusions The oxygen glucose deprivation/reoxygenation model of rat's hippocampal neurons in vitro was established successfully. From the findings of morphological changes and apoptosis rate of

  13. Marked differences in drug-induced methemoglobinemia in sheep are not due to RBC glucose-6-phosphate dehydrogenase, reduced glutathione, or methemoglobin reductase activity

    Energy Technology Data Exchange (ETDEWEB)

    Martin, D.G.; Guertler, A.T.; Lagutchik, M.S.; Woodard, C.L.; Leonard, D.A.

    1993-05-13

    Benzocaine is a commonly used topical anesthetic that is structurally similar to current candidates for cyanide prophylaxis. Benzocaine induces profound methemoglobinemia in some sheep but not others. After topical benzocaine administration certain sheep respond to form MHb (elevated MHb 16-50% after a 56-280 mg dose, a 2-10 second spray with benzocine), while other phenotypically similar sheep fail to significantly form MHb (less than a 2% increase from baseline). Deficiencies in Glucose-6-phosphate dehydrogenase (G-6-PD), reduced glutathione (GSH), and MHb reductase increase the susceptibility to methemoglobinemia in man and animals. Sheep are used as a model for G-6-PD deficiency in man, and differences in this enzyme level could cause the variable response seen in these sheep. Similarly, differences in GSH and MHb reductase could be responsible for the observed differences in MHb formation.

  14. Glucose-6-phosphate dehydrogenase Guadalajara--a case of chronic non-spherocytic haemolytic anaemia responding to splenectomy and the role of splenectomy in this disorder.

    Science.gov (United States)

    Hamilton, J W; Jones, F G C; McMullin, Mary Frances

    2004-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme of the pentose phosphate shunt pathway a major function of which is to prevent cellular oxidative damage. Deficiency in red blood cells is associated with a number of varied clinical manifestations. Chronic non-spherocytic haemolytic anaemia is uncommon but is usually characterized by chronic haemolysis, often with severe anaemia. In the past splenectomy in this condition has been thought to be of questionable benefit. We report a case of G6PD Guadalajara where splenectomy produced transfusion independence and have reviewed the literature. Those cases with exon 10 mutations often have a severe clinical phenotype, which responds to splenectomy. This procedure should be considered in this condition.

  15. [Frequency of color blindness and glucose-6-phosphate dehydrogenase enzyme deficiency in non-industrialized populations in the state of Nuevo León, México].

    Science.gov (United States)

    Ceda-Flores, R M; Arriaga-Ríos, G; Muñoz-Campos, J; Bautista-Peña, V A; Angeles Rojas-Alvarado, M; González-Quiróga, G; Leal-Garza, C H; Garza-Chapa, R

    1990-01-01

    In order to know if there would be genetic structural differences among non industrial and industrial populations, two genetic markers were studied: color-blindness (CPC) and glucose-6-phosphate dehydrogenase deficiency (G6PD), in students, males and females that were resident in five non industrial populations in the State of Nuevo Leon. The results were compared with the information for industrial zone from the Monterrey Metropolitan area (AMM). It was found that the frequencies of CPC and G6PD in non industrial populations (2.57 and 0.00 per cent), were lower than the ones in the industrial AMM (4.0 and 0.66 per cent), probably as a result that in the first populations, with minor urbanization, the main factors that influence are: natural selection, interacial mixed or genetic drift and the second population is the immigration, since 1940 to present time, of Mexican populations with greater influence from the Indians and Africans.

  16. Oxidative stress in patients with nongenital warts.

    Science.gov (United States)

    Sasmaz, Sezai; Arican, Ozer; Kurutas, Ergul Belge

    2005-08-31

    Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male) and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (Pstress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

  17. Glucose-6 phosphate dehydrogenase deficiency and psychotic illness

    Directory of Open Access Journals (Sweden)

    Vijender Singh

    2012-01-01

    Full Text Available Mr. T, a 28-year-old unmarried male, a diagnosed case of Glucose-6 Phosphate Dehydrogenase (G6PD deficiency since childhood, presented with 13 years of psychotic illness and disturbed biological functions. He showed poor response to antipsychotics and mood stabilizers and had three prior admissions to Psychiatry. There was a family history of psychotic illness. The General Physical Examination and Systemic Examination were unremarkable. Mental Status Examination revealed increased psychomotor activity, pressure of speech, euphoric affect, prolixity, delusion of persecution, delusion of grandiosity, delusion of control, thought withdrawal and thought insertion, and second and third person auditory hallucinations, with impaired judgment and insight. A diagnosis of schizophrenia paranoid type, with a differential diagnosis of schizoaffective disorder manic subtype, was made. This case is being reported for its rarity and atypicality of clinical presentation, as well as a course of psychotic illness in the G6PD Deficiency state,with its implications on management.

  18. Modelo teórico para explicar la acumulación de gotas lipídicas en embriones bovinos machos o hembras producidos in vitro

    OpenAIRE

    OLIVERA MARTHA; CAMARGO OMAR; RUIZ TATIANA

    2008-01-01

    La glucosa 6-fosfato deshidrogenasa (G6PD), codificada por un gen ubicado en el cromosoma X, es la enzima limitante de vía de las pentosas fosfato (PF). La entrada de la glucosa así como su flujo y el rendimiento metabólico de esta vía están determinados tanto por los mismos niveles glucosa así como por la actividad de la G6PD. Por esta vía, la glucosa regula la trascripción de varios genes lipogénicos. En algunos embriones hembra producidos in vitro, se regis...

  19. Can affinity interactions influence the partitioning of glucose-6-phosphate dehydrogenase in two-phase aqueous micellar systems?

    Directory of Open Access Journals (Sweden)

    André M. Lopes

    2008-01-01

    Full Text Available In this work, we provide an investigation of the role and strength of affinity interactions on the partitioning of the glucose-6-phosphate dehydrogenase in aqueous two-phase micellar systems. These systems are constituted of micellar surfactant solutions and offer both hydrophobic and hydrophilic environments, providing selectivity to biomolecules. We studied G6PD partitioning in systems composed of the nonionic surfactants, separately, in the presence and absence of affinity ligands. We observed that G6PD partitions to the micelle-poor phase, owing to the strength of excluded-volume interactions in these systems that drive the protein to the micelle-poor phase, where there is more free volume available.

  20. Prevalence of anemia, iron deficiency, thalassemia and glucose-6-phosphate dehydrogenase deficiency among hill-tribe school children in Omkoi District, Chiang Mai Province, Thailand.

    Science.gov (United States)

    Yanola, Jintana; Kongpan, Chatpat; Pornprasert, Sakorn

    2014-07-01

    The prevalaence of anemia, iron deficiency, thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were examined among 265 hill-tribe school children, 8-14 years of age, from Omkoi District, Chiang Mai Province, Thailand. Anemia was observed in 20 school children, of whom 3 had iron deficiency anemia. The prevalence of G-6-PD deficiency and β-thalassemia trait [codon 17 (A>T), IVSI-nt1 (G>T) and codons 71/72 (+A) mutations] was 4% and 8%, respectively. There was one Hb E trait, and no α-thalassemia-1 SEA or Thai type deletion. Furthermore, anemia was found to be associated with β-thalassemia trait in 11 children. These data can be useful for providing appropriate prevention and control of anemia in this region of Thailand.

  1. Variations of the enzymatic activity of the rat's gum glycolytic cycle following administration of sweeteners.

    Science.gov (United States)

    Seri, S; D'Alessandro, A; Seri, M

    1995-01-01

    The effects of saccharose and isomalt on the rat's gum carbohydrate metabolism have been studied through evaluation of the activity of hexokinase (HK), phosphoglucoisomerase (PGI), lactatedehydrogenase (LDH), glucose-6-phosphate-dehydrogenase (G6PD), phosphofructokinase (PFK) and phosphoglucomutase (PGM). The values obtained by administering a drink sweetened with 10% isomalt are significantly lower (p isomalt on the rat's gum glycolytic cycle enzymes was found to be lower than that detected for other polyalcohols.

  2. The regulation of the oxidative phase of the pentose phosphate pathway: new answers to old problems.

    Science.gov (United States)

    Barcia-Vieitez, Ramiro; Ramos-Martínez, Juan Ignacio

    2014-11-01

    There is a paradox in the oxidizing phase of the phosphate pentose pathway that has not yet been solved. The flow through the pathway is reduced in basal conditions; however, it must rise notably when a NADPH supplement is required. The paradox consists of the strong inhibition that the NADPH exerts on the both dehydrogenases of the pathway, especially on the regulating enzyme glucose-6-phosphate dehydrogenase (G6PD). Theoretically, in anabolic situations, the increase of gene expression of G6PD and 6-phosphogluconate dehydrogenase can induce a rise in the production of NADPH, which would cause the immediate inhibition of the enzyme and a drastic flow reduction. However, increasing the flow through oxidative phase of the pentose phosphate pathway (OPPP) has been experimentally demonstrated in many physiological states. However, this situation will be resolved if the NADPH metabolized or otherwise sufficient NADPH is sequestered to relax the inhibition of the dehydrogenases of OPPP and to maintain high ratio of NADPH/NADP(+) needed to ensure the reducing environment of the cell cytoplasm and the contribution of NADPH for anabolic processes. In 1974, the presence of a protein capable of reversing the inhibition of G6PD by NADPH was detected; however, to date, this paradox remains undisclosed. This review deals with the possibility that such reverting action might be similar to the activity of a protein named HSCARG, which is responsible for the abduction of NADPH, thus keeping a portion of the coenzyme away from the catalytic action and, simultaneously, the immune response through the NF-κB (nuclear factor kappa light-chain enhancer of activated B cells) system. The model has many similarities with the hypothesis proposed some 40 years back on the reversion of G6PD inhibition by NADPH.

  3. Drug Resistance in Malaria. Investigation of Mechanisms and Patterns of Drug Resistance and Cross Resistance in Malaria.

    Science.gov (United States)

    1985-01-31

    deficiency (Brewer, Tarlov , and Kellermeyer, 1961) who are not in hemolytic crisis. Similarly, as there is evidence of a decrease in G6PD activity with...Invest. 59, 633. Armbrecht, H. J., Birnbaum, L. S., Zenser, T. V., and Davis, B. B. (1982). Changes in hepatic microsomal membrane fluidity with age...for pyruvate kinase deficiency, glucose 6-phosphate dehydrogenase deficiency, and glutathione reductase deficiency. Blood 28, 553. Brewer, G. J., Tarlov

  4. The NADPH metabolic network regulates human αB-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Heng B Xie

    2013-06-01

    Full Text Available Dominant mutations in the alpha-B crystallin (CryAB gene are responsible for a number of inherited human disorders, including cardiomyopathy, skeletal muscle myopathy, and cataracts. The cellular mechanisms of disease pathology for these disorders are not well understood. Among recent advances is that the disease state can be linked to a disturbance in the oxidation/reduction environment of the cell. In a mouse model, cardiomyopathy caused by the dominant CryAB(R120G missense mutation was suppressed by mutation of the gene that encodes glucose 6-phosphate dehydrogenase (G6PD, one of the cell's primary sources of reducing equivalents in the form of NADPH. Here, we report the development of a Drosophila model for cellular dysfunction caused by this CryAB mutation. With this model, we confirmed the link between G6PD and mutant CryAB pathology by finding that reduction of G6PD expression suppressed the phenotype while overexpression enhanced it. Moreover, we find that expression of mutant CryAB in the Drosophila heart impaired cardiac function and increased heart tube dimensions, similar to the effects produced in mice and humans, and that reduction of G6PD ameliorated these effects. Finally, to determine whether CryAB pathology responds generally to NADPH levels we tested mutants or RNAi-mediated knockdowns of phosphogluconate dehydrogenase (PGD, isocitrate dehydrogenase (IDH, and malic enzyme (MEN, the other major enzymatic sources of NADPH, and we found that all are capable of suppressing CryAB(R120G pathology, confirming the link between NADP/H metabolism and CryAB.

  5. The NADPH metabolic network regulates human αB-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster.

    Science.gov (United States)

    Xie, Heng B; Cammarato, Anthony; Rajasekaran, Namakkal S; Zhang, Huali; Suggs, Jennifer A; Lin, Ho-Chen; Bernstein, Sanford I; Benjamin, Ivor J; Golic, Kent G

    2013-06-01

    Dominant mutations in the alpha-B crystallin (CryAB) gene are responsible for a number of inherited human disorders, including cardiomyopathy, skeletal muscle myopathy, and cataracts. The cellular mechanisms of disease pathology for these disorders are not well understood. Among recent advances is that the disease state can be linked to a disturbance in the oxidation/reduction environment of the cell. In a mouse model, cardiomyopathy caused by the dominant CryAB(R120G) missense mutation was suppressed by mutation of the gene that encodes glucose 6-phosphate dehydrogenase (G6PD), one of the cell's primary sources of reducing equivalents in the form of NADPH. Here, we report the development of a Drosophila model for cellular dysfunction caused by this CryAB mutation. With this model, we confirmed the link between G6PD and mutant CryAB pathology by finding that reduction of G6PD expression suppressed the phenotype while overexpression enhanced it. Moreover, we find that expression of mutant CryAB in the Drosophila heart impaired cardiac function and increased heart tube dimensions, similar to the effects produced in mice and humans, and that reduction of G6PD ameliorated these effects. Finally, to determine whether CryAB pathology responds generally to NADPH levels we tested mutants or RNAi-mediated knockdowns of phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (IDH), and malic enzyme (MEN), the other major enzymatic sources of NADPH, and we found that all are capable of suppressing CryAB(R120G) pathology, confirming the link between NADP/H metabolism and CryAB.

  6. The burden and consequences of inherited blood disorders among young children in western Kenya.

    Science.gov (United States)

    Suchdev, Parminder S; Ruth, Laird J; Earley, Marie; Macharia, Alex; Williams, Thomas N

    2014-01-01

    Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6-35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, -3.7 kb alpha-globin chain deletion, glucose-6-phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for α(+) -thalassaemia. The Hp 2-2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P = 0.005). After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L(-1) ), iron deficiency (ferritin children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common among pre-school children in western Kenya and are important contributors to anaemia. © 2012 JohnWiley & Sons Ltd.

  7. Global distribution of consanguinity and their impact on complex diseases: Genetic disorders from an endogamous population

    Directory of Open Access Journals (Sweden)

    Abdulbari Bener

    2017-10-01

    Conclusion: The present study revealed a higher incidence of certain diseases in consanguineous population with a high significant increase in the prevalence of common adult diseases such as diabetes mellitus, cancer, blood disorders, mental disorders, heart diseases, asthma, gastro-intestinal disorders, hypertension, hearing deficit, G6PD and common eye diseases. This confirms the role of genetic factors across the full spectrum of disease and not only for Mendelian disorders.

  8. Human enzyme polymorphism in the Canary Islands. III. Tenerife Island population.

    Science.gov (United States)

    Afonso, J M; Hernández, M; Larruga, J M; Cabrera, V M; González, A M

    1989-08-01

    We analyzed the genetic polymorphism of eight red cell enzymes in samples from different geographical areas of Tenerife and the Iberian peninsula. The gene frequency heterogeneity found within the Tenerife samples was at the same level as that of Tenerife-mainland comparisons. The presence of the Negroid G6PD A+ allele in the Tenerife samples is evidence of an African admixture with a mean estimation of 4.5%.

  9. Case Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors

    Science.gov (United States)

    2009-01-01

    CBC, reticulocyte count, G-6-PD determination, Duffy phenotype, ABO and Rh group typing, hemoglobin electrophoresis and erythrocyte sedimentation...was considered as an exclusion criterion. Tests for hemoglobin , white blood cell count, platelet count, and total bilirubin were performed again on...malaria-naïve volunteers were randomly allocated to Groups A–C and exposed to 3 ± 1, 6 ± 1, and 9 ± 1 bites of Anopheles albimanus mosquitoes infected

  10. Glutathione metabolism and glucose 6-phosphate dehydrogenase activity in experimental liver injury.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-12-01

    Full Text Available Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44 in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH following an intragastric administration of carbon tetrachloride (CCl4 to rats. Oxidized glutathione (GSSG also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2., glutathione peroxidase (EC 1.11.1.9 and malic enzyme (EC 1.1.1.40 activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2 activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.

  11. Individual and environmental risk factors for dengue and chikungunya seropositivity in North-Eastern Tanzania

    DEFF Research Database (Denmark)

    Kajeguka, Debora C.; Msonga, Maulid; Schiøler, Karin L.

    2017-01-01

    Background: Dengue and chikungunya are mosquito-borne viral diseases of major global health concern. In Tanzania, information on risk factors for dengue and chikungunya is limited. We investigated individual, household, socio-economic, demographic and environmental risk factors for dengue...... of uncovered containers that may serve as breeding sites for mosquitoes, avoiding animal husbandry in the peri-domestic environment and clearing of vegetation surrounding houses. More studies are needed to investigate the association of dengue and G6PD deficiency....

  12. Two-phase aqueous micellar systems: an alternative method for protein purification

    Directory of Open Access Journals (Sweden)

    Rangel-Yagui C. O.

    2004-01-01

    Full Text Available Two-phase aqueous micellar systems can be exploited in separation science for the extraction/purification of desired biomolecules. This article reviews recent experimental and theoretical work by Blankschtein and co-workers on the use of two-phase aqueous micellar systems for the separation of hydrophilic proteins. The experimental partitioning behavior of the enzyme glucose-6-phosphate dehydrogenase (G6PD in two-phase aqueous micellar systems is also reviewed and new results are presented. Specifically, we discuss very recent work on the purification of G6PD using: i a two-phase aqueous micellar system composed of the nonionic surfactant n-decyl tetra(ethylene oxide (C10E4, and (ii a two-phase aqueous mixed micellar system composed of C10E4 and the cationic surfactant decyltrimethylammonium bromide (C10TAB. Our results indicate that the two-phase aqueous mixed (C10E4/C10TAB micellar system can improve significantly the partitioning behavior of G6PD relative to that observed in the two-phase aqueous C10E4 micellar system.

  13. TAp73 enhances the pentose phosphate pathway and supports cell proliferation.

    Science.gov (United States)

    Du, Wenjing; Jiang, Peng; Mancuso, Anthony; Stonestrom, Aaron; Brewer, Michael D; Minn, Andy J; Mak, Tak W; Wu, Mian; Yang, Xiaolu

    2013-08-01

    TAp73 is a structural homologue of the pre-eminent tumour suppressor p53. However, unlike p53, TAp73 is rarely mutated, and instead is frequently overexpressed in human tumours. It remains unclear whether TAp73 affords an advantage to tumour cells and if so, what the underlying mechanism is. Here we show that TAp73 supports the proliferation of human and mouse tumour cells. TAp73 activates the expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). By stimulating G6PD, TAp73 increases PPP flux and directs glucose to the production of NADPH and ribose, for the synthesis of macromolecules and detoxification of reactive oxygen species (ROS). The growth defect of TAp73-deficient cells can be rescued by either enforced G6PD expression or the presence of nucleosides plus an ROS scavenger. These findings establish a critical role for TAp73 in regulating metabolism, and connect TAp73 and the PPP to oncogenic cell growth.

  14. Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

    Energy Technology Data Exchange (ETDEWEB)

    Martin del Campo, Julia S. [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico); Patino, Rodrigo, E-mail: rtarkus@mda.cinvestav.mx [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico)

    2011-04-20

    Research highlights: {yields} The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. {yields} A spectrophotometric method is proposed for kinetic and thermodynamic analysis. {yields} The pH and the temperature influences are reported on physical chemical properties. {yields} Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD{sub ox}) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD{sub ox} as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, {Delta}{sub f}G{sup o} = -1784 {+-} 5 kJ mol{sup -1}.

  15. Alleviation of PEGylated Puerarin on Erythrocyte Hemolysis Induced by Puerarin in Glucose-6-phosphate Dehydrogenase-deficient Rats

    Institute of Scientific and Technical Information of China (English)

    LIU; Xin-yi; LI; Jian-rong; WANG; Nai-jie; ZHANG; Guang-ping; DU; Feng; YE; Zu-guang; XIANG; Da-xiong

    2013-01-01

    Objective To explore and analyze the reducing hemolytic effects of PEGylated puerarin (PEG-PUE) on erythrocytes induced by PUE in glucose-6-phosphate dehydrogenase (G6PD)-deficient rats. Methods The rat model with G6PD-deficiency was established via sc injecting 1% acetylphenyl-hydrazine. Then the G6PD-deficient erythrocyte suspension obtained from this rat model was used to evaluate the hemolytic effects of PUE and the reducing hemolytic effects of PEG-PUE via hemolytic activity and erythrocyte osmotic fragility assay. Results It was found that PUE could cause a serious hemolysis to the erythrocyte suspension with the increase of drug concentration and the prolongation of drug incubation time, the hemolytic rate of PUE was up to 40%, while the addition of PEG-PUE to the erythrocyte suspension revealed no significant hemolysis. Additionally, the result of erythrocyte osmotic fragility indicated that PEG-PUE exerted a slight effect on the erythrocyte membranes, and the NaCl concentration that induced 50% hemolysis (32 mmol/L) was about one-third PUE. Conclusion These results demonstrate that PEG-PUE could play a significant role in reducing the side effect of hemolysis induced by PUE. The low hemolytic activity of PEG-PUE makes it a favorable candidate for in vivo tests and PEG-PUE could also provide the useful insight for the further formulation development as an innovative drug.

  16. Alleviation of PEGylated Puerarin on Erythrocyte Hemolysis Induced by Puerarin in Glucose-6-phosphate Dehydrogenase-deficient Rats

    Institute of Scientific and Technical Information of China (English)

    LIU Xin-yi; LI Jian-rong; WANG Nai-jie; ZHANG Guang-ping; DU Feng; YE Zu-guang; XIANG Da-xiong

    2013-01-01

    Objective To explore and analyze the reducing hemolytic effects of PEGylated puerarin (PEG-PUE) on erythrocytes induced by PUE in glucose-6-phosphate dehydrogenase (G6PD)-deficient rats.Methods The rat model with G6PD-deficiency was established via sc injecting 1% acetylphenyl-hydrazine.Then the G6PD-deficient erythrocyte suspension obtained from this rat model was used to evaluate the hemolytic effects of PUE and the reducing hemolytic effects of PEG-PUE via hemolytic activity and erythrocyte osmotic fragility assay.Results It was found that PUE could cause a serious hemolysis to the erythrocyte suspension with the increase of drug concentration and the prolongation of drug incubation time,the hemolytic rate of PUE was up to 40%,while the addition of PEG-PUE to the erythrocyte suspension revealed no significant hemolysis.Additionally,the result of erythrocyte osmotic fragility indicated that PEG-PUE exerted a slight effect on the erythrocyte membranes,and the NaCl concentration that induced 50% hemolysis (32 mmol/L) was about one-third PUE.Conclusion These results demonstrate that PEG-PUE could play a significant role in reducing the side effect of hemolysis induced by PUE.The low hemolytic activity of PEG-PUE makes it a favorable candidate for in vivo tests and PEG-PUE could also provide the useful insight for the further formulation development as an innovative drug.

  17. Reappraisal of known malaria resistance loci in a large multi-centre study

    Science.gov (United States)

    Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

    2015-01-01

    Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933

  18. Data on how several physiological parameters of stored red blood cells are similar in glucose 6-phosphate dehydrogenase deficient and sufficient donors

    Directory of Open Access Journals (Sweden)

    Vassilis L. Tzounakas

    2016-09-01

    Full Text Available This article contains data on the variation in several physiological parameters of red blood cells (RBCs donated by eligible glucose-6-phosphate dehydrogenase (G6PD deficient donors during storage in standard blood bank conditions compared to control, G6PD sufficient (G6PD+ cells. Intracellular reactive oxygen species (ROS generation, cell fragility and membrane exovesiculation were measured in RBCs throughout the storage period, with or without stimulation by oxidants, supplementation of N-acetylcysteine and energy depletion, following incubation of stored cells for 24 h at 37 °C. Apart from cell characteristics, the total or uric acid-dependent antioxidant capacity of the supernatant in addition to extracellular potassium concentration was determined in RBC units. Finally, procoagulant activity and protein carbonylation levels were measured in the microparticles population. Further information can be found in “Glucose 6-phosphate dehydrogenase deficient subjects may be better “storers” than donors of red blood cells” [1].

  19. Deficiencia de glucosa 6 fosfato deshidrogenasa: análisis enzimático y molecular en una población de Bogotá

    Directory of Open Access Journals (Sweden)

    Magda Carolina Sánchez

    2008-06-01

    Full Text Available bjetivo: Determinar qué tan frecuente es la deficiencia de glucosa 6 fosfato deshidrogenasa (G6PD y realizar análisis molecular para identificar las variantes A+, A- y mediterránea en una población de residentes en Bogotá.Métodos: Se analizaron 348 personas que residen en Bogotá, pertenecientes a la Policía Nacional y a la Universidad del Rosario. La actividad enzimática se determinó en muestras de sangre mediante espectrofotometría con el kit Trinity Biotech (Cat 345-B. Los valores de hemoglobina (Hg y hematócrito (Hto se determinaron con el método de Drabkin y sedimentación, respectivamente. La determinación de las variantes moleculares se realizó mediante amplificación por reacción en cadena de la polimerasa (PCR y análisis de fragmentos de restricción de longitud polimórfica (RFLP con las enzimas NlaIII, Fok I y MboII para A+, A- y mediterránea, respectivamente. Se hicieron análisis estadísticos para comparar la concentración de Hg en personas sanas y deficientes, la actividad de G6PD por géneros y los datos de frecuencia a nivel mundial.Resultados y conclusiones: La frecuencia de deficiencia de G6PD para la población en estudio fue 3.1%. En 1.4% de los casos se observó actividad deficiente, en 1.7% actividad intermedia y en 0.6% actividad aumentada. No se encontraron las variantes moleculares A+, A- y mediterránea en ningún afectado. La actividad de G6PD no tuvo diferencias por género. Se encontró diferencia significativa en el valor de hemoglobina entre las personas sanas y deficientes de G6PD. Los individuos deficientes eran asintomáticos lo que indica mecanismos de compensación de estrés oxidativo. Las mujeres deficientes son heterocigotos con una inactivación preferencial del cromosoma X anormal y al ser portadoras tienen riesgo de 50% de tener hijos afectados con la enfermedad. La identificación de mujeres y hombres deficientes permite establecer medidas preventivas ante posibles crisis hemol

  20. Hemólisis inducida por el ejercicio: relación entre el nivel de actividad de la glucosa-6-fosfato deshidrogenasa y el grado de hemólisis

    Directory of Open Access Journals (Sweden)

    Javier F. Bonilla

    2008-06-01

    Full Text Available Introducción: La oxidación, al igual que la hemólisis asociadas con el ejercicio tanto moderado como extenuante han sido condiciones objeto de múltiples estudios, pero sólo en algunos recientes se evaluó cómo las variaciones en la capacidad de los mecanismos antioxidantes enzimáticos eritrocitarios específicos y genéticamente determinados, condicionan distintos grados de susceptibilidad a la hemólisis inducida por el ejercicio, pero esos trabajos se han hecho sobre todo en individuos no sedentarios y con deficiencia franca de la enzima G6PD.Objetivo: El propósito de este trabajo fue determinar si existe o no relación entre el nivel de actividad de la enzima eritrocitaria G6PD y el grado de hemólisis inducida por el ejercicio en hombres adultos sedentarios en apariencia sanos, luego de un tiempo experimental de ejercicio moderado pre-extenuante y equivalente en modalidad y magnitud. Metodología: Se evaluaron 25 voluntarios hombres, sedentarios, en apariencia sanos; se les aplicó una sesión de ejercicio, sobre un cicloergómetro, de una hora de duración, a 70% del VO2pico previamente hallado. Sobre la base de la concentración de hemoglobina plasmática se calculó el porcentaje de hemólisis y la haptoglobina consumida, tomando en cuenta la variación en el plasma de la haptoglobina y la hemólisis intravascular inmediatamente después y hasta tres horas luego del ejercicio. Resultados: Se pudo determinar que los individuos presentaron, con base en la determinación de Hb plasmática libre, % de hemólisis y consumo de haptoglobina, hemólisis intravascular durante y hasta por lo menos tres horas post-ejercicio. Conclusiones: La magnitud de la hemólisis presentada, por un lado, tuvo una relación inversa significativa con la actividad de la G6PD, y por otro, que tal magnitud tuvo un comportamiento significativamente distinto por debajo del percentil 40 de la actividad hallada para G6PD y por encima de la misma, o sea, la

  1. Epidemiology and Risk Factors for Neonatal Jaundice in Infants Admitted to NICU of Imam Sajjad Hospital, Yasooj

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    Z. Mahmodi

    2016-01-01

    Full Text Available Introduction & Objective: Jaundice is a common problem in infants in the first days after birth. Jaundice due to serious complications such as kernicterus requires special attention. The objective of this study was to determine the prevalence and risk factors affecting neonatal jaundice. Material & Methods: In this cross-sectional study of 579 infants admitted to the Imam Sajjad Yasouj hospital in 2014 were studied using, convenience non_probability sampling method. By reviewing data type and RH, hemoglobin, G6PD, direct Coombs test - total bilirubin, unconjugated bilirubin was extracted. Gender, weight, gestational age, Apgar score, method of delivery, number of previous breast feeding and jaundice in infants were examined. Using SPSS software, descriptive statistics and independent t-test, ANOVA and chi score ,data analysis was performed. Result: In this study on 3461 newborns, 579 infants (72.16% had jaundice. G6PD deficiency in infants was 12.95%. In this study, the prevalence of risk factors for premature yellowing was ABO incompatibility and G6PD deficiency pre-maturity, pottery hematoma, and RH incompatibility, respectively. Of total number of 579 cases, 58.2% were born through normal vaginal delivery and the rest through cesarean section and also 53.2% were boys and the rest were girls. The most common blood groups were A and AB and the most common blood group of mothers was O. The mothers’ mean gestational age was 38± 2 . Among infants with jaundice, 15.9% were premature (35-37week and 3.45% (20 cases suffered from neonatal infections due to their mothers’ infection during pregnancy. There was no significant relationship between sex, type of delivery, birth weight, Apgar score, history of mothers’ drug use in the birth prevalence of premature hepatitis (P> 0.05. But, a significant relationship between the frequency of breast-feeding, pre-maturity, ABO incompatibility and G6PD and jaundice was found (P<0.05. Conclusion: The

  2. Effect of globular domain of adiponectin on pentose phosphate pathway key enzyme of 3T3 adipocyte%脂联素球状结构域对3T3-L1脂肪细胞磷酸戊糖途径关键酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    王彦; 廉如; 陈思思; 高婷婷; 吴彬; 陈显久

    2012-01-01

    Objective To investigate the effect of globular domain of adiponectin (gAd) on pentose phosphate pathway key enzyme of 3T3-L1 adipocytes. Methods Matured 3T3-L1 adipocytes were intervened with gAd, and realtime PCR (RT-PCR) was used to determine the transcription level of glucose-6-phosphatase (G6PD), the key enzyme in pentose phosphate pathway; the changes of transcription level of G6PD were expressed in changes of mRNA levels. All the data were analyzed statistically. Results G6PD transcription level was not different between gAd group and control group. Conclusions gAd promotes the intake of glucose by 3T3-L1 cells, and the catabolism of glucose taken probably was not via the pentose phosphate pathway.Objective To investigate the effect of globular domain of adiponectin (gAd) on pentose phosphate pathway key enzyme of 3T3-L1 adipocytes. Methods Matured 3T3-L1 adipocytes were intervened with gAd, and realtime PCR (RT-PCR) was used to determine the transcription level of glucose-6-phosphatase (G6PD), the key enzyme in pentose phosphate pathway; the changes of transcription level of G6PD were expressed in changes of mRNA levels. All the data were analyzed statistically. Results G6PD transcription level was not different between gAd group and control group. Conclusions gAd promotes the intake of glucose by 3T3-L1 cells, and the catabolism of glucose taken probably was not via the pentose phosphate pathway.%目的:通过探讨脂联素球状结构域(gAd)对3T3-L1脂肪细胞磷酸戊糖途径关键酶表达的影响,进而探讨gAd促进脂肪细胞摄取的葡萄糖是否经磷酸戊糖途径代谢.方法:用gAd干预分化成熟的3T3-L1脂肪细胞,干预结束后测定细胞残液的葡萄糖浓度,并以实时荧光定量PCR(RT-PCR)法检测各组细胞磷酸戊糖途径关键酶葡萄糖-6-磷酸酶(G6PD)转录水平的表达情况,进行统计学分析.结果:各实验组细胞残液中葡萄糖浓度均显著低于对照组(均P<O.01);各实验组G6PD

  3. EXPRESSION OF MATRIX METALLOPROTEINASE-9 IN HUMANABDOMINAL AORTIC ANEURYSMAL TISSUES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Abdominal aortic aneuryzms(AAAs)are char-acterized by the degradation of structural proteins,including both collagen and elastin and remodelingof the extracellular matrix(ECM).The matrixmetalloproteinases(MMPs)are responsible for col-lagen and elastin degradation withinthe aortic wall.Up to date,14MMPs have beenidentified.Amongthem,in particular,MMP-9(92-kDtypeⅣcolla-genase)shows strong elastinolytic activity[1].Recentstudies showedthat elevated plasmalevel of MMP-9wasassociated with AAAs,i mplicating its p...

  4. 昆明地区29527例新生儿葡萄糖-6-磷酸脱氢酶水平分析

    Institute of Scientific and Technical Information of China (English)

    章印红; 朱姝; 李利; 朱宝生; 张杰; 陈红; 王瑞红; 李苏云

    2014-01-01

    目的 了解昆明地区新生儿葡萄糖-6-磷酸脱氢酶(G6PD)水平,以辅助筛查新生儿G6PD 缺乏症。方法 采集昆明地区29527例新生儿足跟血滤纸片干血斑标本,采用荧光分析法检测 G6PD 水平。采用SPSS13.0统计软件进行数据分析。结果 29527例滤纸片干血斑标本的G6PD水平为0.10~ 15.95 U/gHb,平均为(6.18±1.04)U/g Hb。男、女新生儿 G6PD 水平分别为(6.16 ±1.10)U/g Hb和(6.21 ±1.00)U/gHb,男女G6PD水平比较差异有统计学意义(t= -4.095,P 〈0.05);按不同采血年龄分为3组,分别为〈3 d采血组、3~7 d采血组和8~28 d采血组,其G6PD水平分别为(6.13±1.05)U/gHb、(6.20±1.03)U/gHb和(6.13±1.07)U/gHb。 〈3 d采血组和8~28 d采血组间 G6PD 水平比较差异无统计学意义(t=0.029,P 〉0.05),这2组G6PD水平与3~7 d组比较差异均有统计学意义(P均 〈0.05),且 G6PD 水平均值低于3~7 d组;按不同检测水平分为3组,分别为〈2.20 U/gHb组、2.20~2.60 U/gHb组和 〉2.60 U/gHb组。 〈2.20U/gHb组中男、女新生儿构成比与另外2组比较差异均有统计学意义(P均 〈0.05)。结论 昆明地区 G6PD缺乏症符合X伴性遗传方式,男性检出率高于女性;新生儿期任意时间采血对 G6PD 阳性检出率无影响;昆明地区G6PD缺乏症流行病学有其独特的特点,检出率有下降趋势。

  5. Protective effects of a wheat germ rich diet against the toxic influence of profenofos on rat tissue lipids and oxidative pentose phosphate shunt enzymes

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    Abdel-Rahim, G. A.

    2011-09-01

    Full Text Available The effects of technical and formulated forms of profenofos on the metabolic lipid fractions of the liver, brain and kidneys as well as the activity of glucose-6-phosphate dehydrogenase (G6PD and 6-phosphogluconate dehydrogenase (6PGD, which consider lipid related enzymes, were studied. The two forms of profenofos were given separately either orally or by dermal at doses of 1/20 LD50 for 3 months (one dose every 48 h. Total lipids and lipid fractions (cholesterol, triglycerides and phospholipid contents decreased in the three studied organ tissues either in technical or formulated profenofos-induced rats compared with normal control animals. The highest effect was observed in the case of orally formulated profenofo induction, and the lowest was detected for the dermal technical one. The same trend was found in the activities of G6PD and 6PGD associated with lipid metabolism in the liver, brain and kidney tissues under the same conditions. On other hand, the treatment of profenofos-induced animals by feeding a wheat germ rich diet (as antioxidant agent produced significant improvements in both lipid fraction content and enzyme activity. In addition, the effects of the wheat germ rich diet (α-tocopherol rich source readjusted and improved the disturbed metabolic fractions of the lipid profiles in the profenofos-induced rats as well as their related enzyme activities (G6PD and 6PGD: oxidative pentose phosphate shunt.

    El efecto de formas técnicas o formuladas de profenofós en la fracción lipídica metabólica de hígado, cerebro y riñones así como la actividad de la glucosa-6-fosfato deshidrogenasa (G6PD y 6-fosfogluconato deshidrogenasa (6PGD, que son consideradas enzimas relacionadas con los lípidos, fueron estudiadas. Ambas formas de profenofós fueron suministradas separadamente tanto por vía oral como cutánea a una dosis de 1/20 LD50 durante 3 meses (una dosis cada 48 horas. Los lípidos totales y

  6. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.

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    Eleanor Wheeler

    2017-09-01

    African Americans, the X-linked G6PD G202A variant (T-allele frequency 11% was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96 per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97 in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74 of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

  7. Epidemiology and Control of Plasmodium vivax in Afghanistan

    Science.gov (United States)

    Leslie, Toby; Nahzat, Sami; Sediqi, Walid

    2016-01-01

    Around half of the population of Afghanistan resides in areas at risk of malaria transmission. Two species of malaria (Plasmodium vivax and Plasmodium falciparum) account for a high burden of disease—in 2011, there were more than 300,000 confirmed cases. Around 80–95% of malaria is P. vivax. Transmission is seasonal and focal, below 2,000 m in altitude, and in irrigated areas which allow breeding of anopheline mosquito vectors. Malaria risk is stratified to improve targeting of interventions. Sixty-three of 400 districts account for ∼85% of cases, and are the target of more intense control efforts. Pressure on the disease is maintained through case management, surveillance, and use of long-lasting insecticide-treated nets. Plasmodium vivax treatment is hampered by the inability to safely treat latent hypnozoites with primaquine because G6PD deficiency affects up to 10% of males in some ethnic groups. The risk of vivax malaria recurrence (which may be as a result of reinfection or relapse) is around 30–45% in groups not treated with primaquine but 3–20% in those given 14-day or 8-week courses of primaquine. Greater access to G6PD testing and radical treatment would reduce the number of incident cases, reduce the infectious reservoir in the population, and has the potential to reduce transmission as a result. Alongside the lack of G6PD testing, under-resourcing and poor security hamper the control of malaria. Recent gains in reducing the burden of disease are fragile and at risk of reversal if pressure on the disease is not maintained. PMID:27708189

  8. Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice

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    Melariri P

    2015-02-01

    Full Text Available Paula Melariri,1 Lonji Kalombo,2 Patric Nkuna,2 Admire Dube,2,3 Rose Hayeshi,2 Benhards Ogutu,4,5 Liezl Gibhard,6 Carmen deKock,6 Peter Smith,6 Lubbe Wiesner,6 Hulda Swai2 1Polymers and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Port Elizabeth, South Africa; 2Polymer and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Pretoria, South Africa; 3School of Pharmacy, University of the Western Cape, Bellville, South Africa; 4Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 5Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 6Division of Pharmacology, University of Cape Town Medical School, Groote Schuur Hospital, Cape Town, South Africa Abstract: Tafenoquine (TQ, a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD-deficient individuals. A microemulsion formulation of TQ (MTQ with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity

  9. Mean reticulocyte volume: a specific parameter to screen for hereditary spherocytosis.

    Science.gov (United States)

    Xu, Yuchan; Yang, Wang; Liao, Lin; Deng, Zengfu; Qiu, Yuling; Chen, Wenqiang; Lin, Faquan

    2016-02-01

    This study assessed the value of mean reticulocyte volume (MRV) for differential diagnosis of hereditary spherocytosis (HS) so as to develop conventional and new specific screen indexes. Subjects in this study were divided into three groups: 53 cases in HS group, 217 cases in hemolytic anemia control group (109 cases of thalassemia (THAL), 56 cases of glucose-6-phosphate dehydrogenase G6PD deficiency anemia, and 52 cases of autoimmune hemolytic anemia (AIHA)), and 100 cases in healthy control group. We analyzed erythrocyte and reticulocyte parameters including MRV, mean sphered corpuscular volume, mean corpuscular hemoglobin concentration, and immature reticulocyte fraction. Results demonstrated that MRV was significantly lower in the HS group but significantly higher in the AIHA and G6PD deficiency anemia groups than that in the healthy control group (P = 0.000). MRV was not significantly different between the AIHA and G6PD deficiency anemia groups (P = 0.977) and between the healthy control and THAL groups (P = 0.168). The area under the ROC curve of MRV for diagnosis of HS was 0.942, with a standard error of 0.019, 95% confidence interval of 0.905-0.979, and optimal critical diagnosis point of 95.77 fL. When the MRV was ≤95.77 fL, the sensitivity and specificity for diagnosis of HS were 86.80% and 91.20%, respectively. Therefore, MRV is a general and specific new index for screening HS and important for differential diagnosis of different types of hemolytic anemia.

  10. Inherited hemolytic disorders with high occurrence of b-thalassemia in Sindhi community of Jabalpur town in Madhya Pradesh, India

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    RS Balgir

    2010-04-01

    Full Text Available Hereditary hemolytic disorders such as hemoglobin disorders, β-thalassemia syndrome, G6PD deficiency, and ABO and Rhesus blood groups are the most common public health problems in India. Community genetic screening provides multifaceted information for finding prevalence, level of health education, preventive strategies such as genetic/marriage counseling to relieve the burden of vulnerable communities. However, such genetic screening studies are scanty in India. This study aims to find the prevalence of inherited hemolytic disorders in Sindhi community, identify the persons for genetic/marriage counseling and to suggest the relevant strategies for prevention and control to the affected families. A cross-sectional random study of 508 persons of Sindhi community belonging to all ages and both sexes was conducted for screening of hemoglobin disorders, G6PD deficiency and ABO and Rhesus (D blood groups following the standard procedures and techniques from Jabalpur town in Central India. High frequency of β-thalassemia trait (20.5%, Hb D trait (2.2% and hemoglobin D/β-thalassemia (0.2%, G6PD deficiency (0.8%, and a low prevalence of Rhesus negative (3.0% blood group was observed in Sindhi community of Jabalpur town in Madhya Pradesh. A case of β-thalassemia major and Hb D-thalassemia were also encountered. Double heterozygosity of Hb D/β-thalassemia showed hypochromic and microcytic red cell morphology with mild anemia. Inherited hemolytic disorders are an important public health challenge in Sindhi community. Preventive genetics program needs to be vigorously taken up to ameliorate the sufferings of at risk communities in India.

  11. Deficiencia de glucosa-6-fosfato deshidrogenasa en un paciente con síndrome de Down

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    Francisco R. Cammarata Scalisi

    2012-07-01

    Full Text Available El síndrome de Down, es una alteración genética que ocurre cuando un individuo exhibe todo o una parte específica adicional del cromosoma 21 y es la entidad más frecuentemente asociada a retardo mental. La deficiencia de glucosa-6-fosfato deshidrogenasa, es el defecto enzimático más común en humanos y presenta patrón de herencia ligado al cromosoma X recesivo. Se debe a la mutación del gen G6PD, el cual causa diversos fenotipos bioquímicos y clínicos. Reportamos un caso de lactante menor masculino, evaluado en la Unidad de Genética Médica de la Universidad de Los Andes, con el diagnóstico de deficiencia de glucosa-6-fosfato deshidrogenasa con doble mutación A376G y G202A y síndrome de Down con estudio citogenético 47, XY, +21. Palabras clave:Síndrome de Down; deficiencia de glucosa-6-fosfato deshidrogenasa; G6PD; A37G6; G202A. Glucose-6-phosphate dehydrogenase deficiency in a patient with Down syndrome Abstract Down syndrome, is a genetic disorder that occurring when an individual exhibits all or part of an extra copy of chromosome 21 and the most common entity associated mental retardation. Glucose-6-phosphate dehydrogenase deficiency, is the most common human enzyme defect and has a X-linked recessive inheritance. Due to mutations in the G6PD gene, which cause many biochemical and clinical phenotypes. We reported a case of child male, evaluated in the Unit of Medical Genetics of the University of The Andes, with diagnosis of glucose-6-phosphate dehydrogenase deficiency with double mutation A376G and G202A and Down syndrome with cytogenetic study 47, XY, + 21.

  12. Metabolic Signatures of Oxidative Stress and Their Relationship with Erythrocyte Membrane Surface Roughness Among Workers of Manual Materials Handling (MMH).

    Science.gov (United States)

    Ghosh, Subrata; Acharyya, Muktish; Majumder, Titlee; Bagchi, Anandi

    2015-12-01

    Brickfield workers in India perform manual materials handling (MMH) and as a result, are at a high risk of developing oxidative stress. This results in an alteration of the various markers of metabolic oxidative stress at the cellular level. Since red blood cell (RBC) is the central point where oxygen, glucose-6-phosphate dehydrogenase (G-6-PD), and glutathione (GSH) are involved, the surface roughness and its alteration and modeling with respect to workers exposed to MMH may be considered as helpful determinants in predicting early damage to the cell and restoring better health to the exposed population, that is, the worker exposed to stress. Hence, nanometric analysis of the surface roughness of the RBC may serve as an early indicator of the stress-related damage in these individuals. The purpose of the study was to identify early red blood corpuscular surface damage profile in terms of linear modeling correlating various biochemical parameters. Linear modeling has been aimed to be developed in order to demonstrate how individual oxidative stress markers such as malondialdehyde (MDA), G-6-PD, and reduced GSH are related to the RBC surface roughness [root mean square (RMS)]. Conventional analysis of these biochemical responses were evaluated in MMH laborers (age varying between 18 years and 21 years) and a comparable control group of the same age group (with sedentary lifestyles). Peak expiratory flow rate (PEFR) and RBC surface analysis by atomic-force microscopy (AFM) and correlated scanning probe microscopy (SPM-analytical software) with corresponding image analysis were performed immediately after completion of standardized exercise (MMH) at the brickfield. A number of correlated significances and regressive linear models were developed among MDA, G-6-PD, GSH, and RBC surface roughness. It appears that these linear models might be instrumental in predicting early oxidative damages related to specific occupational hazards.

  13. Influence of salts on the coexistence curve and protein partitioning in nonionic aqueous two-phase micellar systems

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    A. M. Lopes

    2014-12-01

    Full Text Available Aqueous two-phase micellar systems (ATPMS can be exploited in separation science for the extraction/purification of desired biomolecules. Prior to phase separation the surfactant solution reaches a cloud point temperature, which is influenced by the presence of electrolytes. In this work, we provide an investigation on the cloud point behavior of the nonionic surfactant C10E4 in the presence of NaCl, Li2SO4 and KI. We also investigated the salts' influence on a model protein partitioning. NaCl and Li2SO4 promoted a depression of the cloud point. The order of salts and the concentration that decreased the cloud point was: Li2SO4 0.5 M > NaCl 0.5 M ≈ Li2SO4 0.2 M. On the other hand, 0.5 M KI dislocated the curve to higher cloud point values. For our model protein, glucose-6-phosphate dehydrogenase (G6PD, partitioning experiments with 0.5 M NaCl or 0.2 M Li2SO4 at 13.85 ºC showed similar results, with K G6PD ~ 0.46. The lowest partition coefficient was obtained in the presence of 0.5 M KI (K G6PD = 0.12, with major recovery of the enzyme in the micelle-dilute phase (%Recovery = 90%. Our results show that choosing the correct salt to add to ATPMS may be useful to attain the desired partitioning conditions at more extreme temperatures. Furthermore, this system can be effective to separate a target biomolecule from fermented broth contaminants.

  14. Effects of x-irradiation on lens reducing systems. [Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Giblin, F.J.; Chakrapani, B.; Reddy, V.N.

    1978-01-01

    Studies have been made of the effects of x ray on various lens reducing systems including the levels of NADPH and glutathione (GSH), the activity of the hexose monophosphate shunt (HMS), and the activities of certain enzymes including glutathion reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase (G-6-PD). It was found that during several weeks following x irradiation but prior to cataract formation there was very little change in the number of reduced -SH groups per unit weight of lens protein but that, with the appearance of cataract, there was a sudden loss of protein -SH groups. In contrast, the concentration of GSH in the x-rayed lens decreased throughout the experimental period. Similarly, the concentration of NADPH in the x-rayed lens was found to decrease significantly relative to controls one week prior to cataract formation and the ratio of NADPH to NADP/sup +/ in the lens shifted at this time period from a value greater than 1.0 in the control lens to less than 1.0 in the x-rayed lens. A corresponding decrease occurred in the activity of the HMS in x-rayed lenses as measured by culture in the presence of 1-/sup 14/C-labelled glucose. G-6-PD was partially inactivated in the x-rayed lens. Of the eight enzymes studied, G-6-PD appeared to be the most sensitive to x-irradiation. The data indicate that x-irradiation results in a steady decrease in the effectiveness of lens reducing systems and that, when these systems reach a critically low point, sudden oxidation of protein -SH groups and formation of high molecular weight protein aggregates may be initiated.

  15. Population genetic study among the Orange Asli (Semai Senoi) of Malaysia: Malayan aborigines.

    Science.gov (United States)

    Saha, N; Mak, J W; Tay, J S; Liu, Y; Tan, J A; Low, P S; Singh, M

    1995-02-01

    A population genetic study was undertaken to provide gene frequency data on the additional blood genetic markers in the Semai and to estimate the genetic relations between the Semai and their neighboring and linguistically related populations by genetic distance and principal components analyses. Altogether 10 polymorphic and 7 monomorphic blood genetic markers (plasma proteins and red cell enzymes) were studied in a group of 349 Senoi Semai from 11 aboriginal settlements (villages) in the Pahang State of western Malaysia. Both the red cell glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) loci reveal the presence of polymorphic frequencies of a nondeficient slow allele at the G6PD locus and a fast allele at the PGD locus. The Semai are characterized by high prevalences of ahaptoglobinemia and G6PD deficiency, high frequencies of HP*1, HB*E, RH*R1, ACP*C, GLO1*1, PGM1*2+, and GC*1F and corresponding low frequencies of ABO*A, HbCoSp, HB*B0, TF*D, CHI, and GC*2. Genetic distance analyses by both cluster and principal components models were performed between the Semai and 14 other populations (Malay; Javanese; Khmer; Veddah; Tamils of Malaysia, Sri Lanka, and India; Sinhalese; Oraon; Toda and Irula of India; Chinese; Japanese; Koreans) on the basis of 30 alleles at 7 polymorphic loci. A more detailed analysis using 53 alleles at 13 polymorphic loci with 10 populations was carried out. Both analyses give genetic evidence of a close relationship between the Semai and the Khmer of Cambodia. Furthermore, the Semai are more closely related to the Javanese than to their close neighbors--the Malay, Chinese, and Tamil Indians. There is no evidence for close genetic relationship between the Semai and the Veddah or other Indian tribes. The evidence fits well with the linguistic relationship of the Semai with the Mon-Khmer branch of the Austro-Asiatic language family.

  16. Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

    Science.gov (United States)

    Tekwani, Babu L.; Herath, H. M. T. Bandara; Sahu, Rajnish; Gettayacamin, Montip; Tungtaeng, Anchalee; van Gessel, Yvonne; Baresel, Paul; Wickham, Kristina S.; Bartlett, Marilyn S.; Fronczek, Frank R.; Melendez, Victor; Ohrt, Colin; Reichard, Gregory A.; McChesney, James D.; Rochford, Rosemary; Walker, Larry A.

    2014-01-01

    Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (−)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (−)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (−)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (−)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (−)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (−)-(R)-PQ may have a better safety margin than the racemate in human. PMID:24913163

  17. Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

    Science.gov (United States)

    Huang, Yang-Yang; Huang, Ching-Shui; Yang, Sien-Sing; Lin, Min-Shung; Huang, May-Jen; Huang, Ching-Shan

    2005-01-01

    AIM: To test the hypothesis that the variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS: Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)6 TAA/A(TA)7TAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, χ2 test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0 ± 6.5 and 12.7 ± 2.9 μmol/L, respectively; Pcholelithiasis in Taiwan Chinese. PMID:16237771

  18. Effects of variant UDP-glucuronosyltransferase 1A1 gene,glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

    Institute of Scientific and Technical Information of China (English)

    Yang-Yang Huang; Ching-Shui Huang; Sien-Sing Yang; Min-Shung Lin; May-Jen Huang; Ching-Shan Huang

    2005-01-01

    AIM: To test the hypothesis that the variant UDPglucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis.METHODS: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups,respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency.RESULTS: Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)6TAA/A(TA)7TAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, χ2 test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0±6.5 and 12.7±2.9 μmol/L, respectively; P<0.001, Student's ttest).CONCLUSION: Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese.

  19. Severe hemophilia A in a female by cryptic translocation: Order and orientation of factor VIII within Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; McGinniss, M.J.; Antonarakis, S.E.; Axelman, J.; Stasiowski, B.A.; Youssoufian, H.; Kearns, W.G.; Chung, A.; Pearson, P.L.; Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (United States)); Muneer, R.S. (Univ. of Oklahoma, Norman (United States))

    1993-04-01

    The authors report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X; 17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1--15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. 27 refs., 5 figs., 1 tab.

  20. Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood.

    Science.gov (United States)

    Raciti, Patricia M; Francis, Richard O; Spitalnik, Patrice F; Schwartz, Joseph; Jhang, Jeffrey S

    2013-08-01

    Red blood cell exchange (RBCEx) is frequently used in the management of patients with sickle cell disease (SCD) and acute chest syndrome or stroke, or to maintain target hemoglobin S (HbS) levels. In these settings, RBCEx is a category I or II recommendation according to guidelines on the use of therapeutic apheresis published by the American Society for Apheresis. Matching donor red blood cells (RBCs) to recipient phenotypes (e.g., C, E, K-antigen negative) can decrease the risk of alloimmunization in patients with multi-transfused SCD. However, this may select for donors with a higher prevalence of RBC disorders for which screening is not performed. This report describes a patient with SCD treated with RBCEx using five units negative for C, E, K, Fya, Fyb (prospectively matched), four of which were from donors with hemoglobin variants and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Pre-RBCEx HbS quantification by high performance liquid chromatography (HPLC) demonstrated 49.3% HbS and 2.8% hemoglobin C, presumably from transfusion of a hemoglobin C-containing RBC unit during a previous RBCEx. Post-RBCEx HPLC showed the appearance of hemoglobin G-Philadelphia. Two units were G6PD-deficient. The patient did well, but the consequences of transfusing RBC units that are G6PD-deficient and contain hemoglobin variants are unknown. Additional studies are needed to investigate effects on storage, in-vivo RBC recovery and survival, and physiological effects following transfusion of these units. Post-RBCEx HPLC can monitor RBCEx efficiency and detect the presence of abnormal transfused units.

  1. Scalable preparation and differential pharmacologic and toxicologic profiles of primaquine enantiomers.

    Science.gov (United States)

    Nanayakkara, N P Dhammika; Tekwani, Babu L; Herath, H M T Bandara; Sahu, Rajnish; Gettayacamin, Montip; Tungtaeng, Anchalee; van Gessel, Yvonne; Baresel, Paul; Wickham, Kristina S; Bartlett, Marilyn S; Fronczek, Frank R; Melendez, Victor; Ohrt, Colin; Reichard, Gregory A; McChesney, James D; Rochford, Rosemary; Walker, Larry A

    2014-08-01

    Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (-)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (-)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (-)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (-)-(R)-PQ may have a better safety margin than the racemate in human.

  2. Impact of red blood cell variants on childhood malaria in Mali: a prospective cohort study

    Science.gov (United States)

    Lopera-Mesa, Tatiana M; Doumbia, Saibou; Konaté, Drissa; Anderson, Jennifer M; Doumbouya, Mory; Keita, Abdoul S; Diakité, Seidina AS; Traoré, Karim; Krause, Michael A; Diouf, Ababacar; Moretz, Samuel E; STullo, Gregory; Miura, Kazutoyo; Gu, Wenjuan; Fay, Michael P; Taylor, Steve M; Long, Carole A; Diakité, Mahamadou; Fairhurst, Rick M

    2015-01-01

    Summary Background Red blood cell (RBC) variants protect African children from severe Plasmodium falciparum malaria. Their individual and interactive impacts on mild disease and parasite density, and their modification by age-dependent immunity, are poorly understood. Methods We conducted a 4-year, prospective cohort study of children aged 0.5–17 years in Maliin 2008-2011. Exposures were haemoglobin S (HbS), HbC, α-thalassaemia, ABO blood groups, and glucose-6-phosphate dehydrogenase (G6PD)deficiency encoded by the X-linked A- allele. Primary and secondary outcomes were malaria incidence and parasite density. Incidence rate ratios (IRRs) were modeled with quasi-Poisson regression; parasite densities were analyzed with Generalized Estimating Equations. Findings We diagnosed 4091 malaria episodes in 1543 children over 2656 child-years of follow-up (cyfu). RBC variants were common: HbAS 14.2%, HbAC 6.7%, α-thalassaemia 28.4%, type O blood group 40.2%, and G6PD deficiency9.4% (boys) and 20.4% (girls). Malaria incidence was 1.54 episodes/cyfu, ranged from 2.78 at age 3 to 0.40 at age 16 years, was reduced 34% in HbAS vs HbAA children (adjusted IRR [aIRR] 0.66; 95% CI 0.59-0.75) and 49% in G6PD A-/A- vs A+/A+ girls (aIRR 0.51; 95% CI 0.29-0.90), but was increased 15% in HbAC children (aIRR 1.15; 95% CI 1.01-1.32). Parasite density was reduced in HbAS vs HbAA children (median 10,550 vs 15, 150 parasites/μL; p=0.0004). HbAS-associated reductions in malaria risk and parasite density were greatest in early childhood. Interpretation Individual and interactive impacts of HbAS, HbAC, and G6PD A-/A-on malaria risk and parasite density define clinical and cellular correlates of protection. Further identification of the molecular mechanisms of these protective effects may uncover novel targets for intervention. Funding Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. PMID:26687956

  3. Comparative analysis on detection of glucose-6-phosphatase deficiency by two different methods.%不同方法检测葡萄糖-6-磷酸酶缺乏的结果分析

    Institute of Scientific and Technical Information of China (English)

    孟宪玲; 范美珍; 杨明山

    2012-01-01

    Objective To compare and evaluate the results of applying two different methods in glu-cose-6-phosphatase (G6PD) deficiency detection. Methods 3 052 blood samples were detected by Spectrophotom-eter assay and Automatic Chemistry analyzer, respectively. Results Of the 3 052 blood samples, 226 cases (7.4%) were detected with G6PD deficiency by Spectrophotometer assay, including 152 males (7.9%) and 71 females (6.3%). By Automatic Chemistry Analyzer, 287 cases (9.4%) were detected with G6PD deficiency, including 182 males (9.5%) and 105 females (9.3%). Conclusion Automatic Chemistry Analyzer and Spectrophotometer assay can both detect G6PD deficiency well, but the former is found with a higher detection rate and easy operation, which is easier to be standardized.%目的 对G6PD缺乏的不同检测方法进行比较和评价.方法 以分光光度计比色法、全自动生化分析仪速率法分别对3 052例来我院婚检和产检人群进行G6PD检测.结果 3 052例受检者中,经分光光度计比色法共检出G6PD缺乏者226例,检出率为7.4%;其中男性152例,检出率为7.9%,女性71例,检出率为6.3%.全自动生化分析仪速率法检出287例,检出率为9.4%;其中男性182例,检出率为9.5%,女性105例,检出率为9.3%.结论 全自动生化分析仪速率法测定G6PD与分光光度计比色法均能很好地检测G6PD缺乏患者,前者的检出率更高,操作便捷快速,更易标准化.

  4. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Science.gov (United States)

    Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei

    2016-01-01

    Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  5. A comparative study of acute intravascular hemolysis in response to two chloroquine-primaquine regimens to treat Plasmodium vivax malaria%两种氯伯喹方案治疗间日疟急性血管内溶血反应比较观察

    Institute of Scientific and Technical Information of China (English)

    孙晓东; 张再兴; 邓艳; 王剑; 魏春; 梁桂亮; 王恒

    2012-01-01

    Objective To compare the safety of an 8-day chloroquine-primaquine regimen and a 14-day chloroquine-primaquine regimen to treat Plasmodium vivax malaria and to explore the relationship between acute intravascular hemolysis (AIH) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Methods A randomized clinical trial was conducted in the City of Laiza, Myanmar and four suburban villages from 2007 to 2008. Patients infected with P. vivax were recruited and randomly divided into groups A and B. Group A received an 8-day chloroquine-primaquine regimen with a total a-dult dose of 1200 mg chloroquine(base, 600 mg on Day 0, 300 mg on Day 1. and 300 mg on Day 2)and 180 mg prima-quine (base, 22. 5 mg primaquine/d×8 d, simultaneously administered with chloroquine on Day 0). Group B received a 14-day chloroquine-primaquine regimen with a total dose of 1 500 mg chloroquine (base, 25 mg chloroquine/kg. body weight×3 d) and 210 mg primaquine (base, 0. 25 mg primaquine/kg. body weight/d×14 d, simultaneously administered with chloroquine on Day 0). Patients were followed up on DO, Dl, D2, D3, D7, D14, D21 and D28; their symptoms, parasite density, body temperature, and urine were observed. Patients who suffered from jaundice and/or hematuria after treatment were deemed to be positive for AIH. G6PD activity was determined using the fluorescent spot test with dried blood specimens on filter paper that were collected from patients enrolled in 2008. Results There were 62 patients in group A; 1 patient from the Jingpo ethnic group developed AIH. The rate of AIH in group A was 1. 67%. There were 56 patients in group B, and none developed AIH. G6PD activity was determined in 74 patients; 11 had G6PD deficiency. The total rate of G6PD deficiency was 14. 87%. The rate of G6PD deficiency was 21. 62% in group A and 8. 11% in group B. The only patient with AIH in group A was found to have a severe G6PD deficiency. There was no significant difference between groups A and B in terms of

  6. Isozyme analysis of Taenia solium isolates from Mexico and Colombia

    Directory of Open Access Journals (Sweden)

    Pablo Maravilla

    2003-12-01

    Full Text Available Mexican and Colombian Taenia solium cysticerci and some species of Taenia adults were assayed using cellulose acetate electrophoresis to distinguish between isolates. Isozyme patterns for ARK, GOT, G3PD, GPI, and MPI were identical in all cysticerci suggesting homozygotic profiles. G6PD and MDH showed different patterns between Mexican and Colombian cysticerci, suggesting regional differences. ME activity was mainly detected in the adult stage suggesting that this enzyme is active in anaerobic environment, while MDH, detected in cysticerci, could be related to an environment that contains oxygen. Finally, the species of taeniid adults analyzed showed different patterns among them.

  7. Priapism and glucose-6-phosphate dehydrogenase deficiency: An underestimated correlation?

    Directory of Open Access Journals (Sweden)

    Aldo Franco De Rose

    2016-10-01

    Full Text Available Priapism is a rare clinical condition characterized by a persistent erection unrelated to sexual excitement. Often the etiology is idiopathic. Three cases of priapism in glucose-6-phosphate dehydrogenase (G6PD deficiency patients have been described in literature. We present the case of a 39-year-old man with glucose- 6-phosphate dehydrogenase deficiency, who reached out to our department for the arising of a non-ischemic priapism without arteriolacunar fistula. We suggest that the glucose-6-phosphate dehydrogenase deficiency could be an underestimated risk factor for priapism.

  8. Hepatoprotective activity of Sphaeranthus amaranthoides on D-galactosamine induced hepatitis in albino rats

    Institute of Scientific and Technical Information of China (English)

    SwarnalathaL; PNeelakanta Reddy

    2012-01-01

    Objective: The plant sphaeranthus amaranthoides Burm.f is used in the district thriunalveli in the treatment of various liver disorders. Methods: in the present study the ethanol extract from sphaeranthus amaranthoides was studied against the D-galactosamine hepatotoxicity. Results: significant hepatoprotective effect was obtained against liver damage induced by the D-galactosamine as evident from changed antioxidant enzymes like CAT, SOD, GPx, GST, GSH, G6PD and GR and a normal architecture of liver and mitochondria compared to toxin controls. Conclusions: the results indicate that ethanol extract of the sphaeranthus amaranthoides could be useful in preventing D-galatosamine induced liver injury.

  9. Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a Negro family.

    Science.gov (United States)

    Prasad, A S; Tranchida, L; Konno, E T; Berman, L; Albert, S; Sing, C F; Brewer, G J

    1968-06-01

    Detailed clinical and genetic studies have been performed in a Negro family, which segregated for sex-linked sideroblastic anemia and glucose-6-phosphate dehydrogenase (G-6-DP) deficiency. This is the first such pedigree reported. Males affected with sideroblastic anemia had growth retardation, hypochromic microcytic anemia, elevated serum iron, decreased unsaturated iron-binding capacity, increased (59)Fe clearance, low (59)Fe incorporation into erythrocytes, normal erythrocyte survival ((51)Cr), normal hemoglobin electrophoretic pattern, erythroblastic hyperplasia of marrow with increased iron, and marked increase in marrow sideroblasts, particularly ringed sideroblasts. Perinuclear deposition of ferric aggregates was demonstrated to be intramitochondrial by electron microscopy. Female carriers of the sideroblastic gene were normal but exhibited a dimorphic population of erythrocytes including normocytic and microcytic cells. The bone marrow studies in the female (mother) showed ringed marrow sideroblasts. Studies of G-6-PD involved the methemoglobin elution test for G-6-PD activity of individual erythrocytes, quantitative G-6-PD assay, and electrophoresis. In the pedigree, linkage information was obtained from a doubly heterozygous woman, four of her sons, and five of her daughters. Three sons were doubly affected, and one was normal. One daughter appeared to be a recombinant. The genes appeared to be linked in the coupling phase in the mother. The maximum likelihood estimate of the recombination value was 0.14. By means of Price-Jones curves, the microcytic red cells in peripheral blood were quantitated in female carriers. The sideroblast count in the bone marrow in the mother corresponded closely to the percentage of microcytic cells in peripheral blood. This is the second example in which the cellular expression of a sex-linked trait has been documented in the human red cells, the first one being G-6-PD deficiency. The coexistence of the two genes in doubly

  10. Neuroprotección en un nuevo modelo de animal transgénico

    OpenAIRE

    Mejías Estévez, Rebeca María

    2006-01-01

    El objetivo general de este proyecto fue analizar en un modelo de parkinsonismo experimental en ratones, si el aumento del poder reductor de forma selectiva en las neuronas dopaminérgicas nigrostriatales (neuronas DNS9, mediante la sobre-expresión del enzima glucosa-6-fosfato deshidrogenada (G6PD), les confiere protección. Además nos interesó estudiar algunos aspectos relacionados con la regulación de la expresión de dicho enzima en células excitables. Los objetivos específicos de este tra...

  11. Isoenzymatic and cytological studies of some Asiatic species of the genus Salsola

    Directory of Open Access Journals (Sweden)

    Aleksandra Wojnicka-Półtorak

    2014-01-01

    Full Text Available The genetic and cytological variability of population of three Salsola species from Asia was investigated, using isozyme electrophoresis and haematoxylin staining. Eight enzyme systems, representing 14-17 loci, were examined: 6PGD, DIA, G6PD, GDH, GOT, MDH, PGM and PGI. Analysis of the chromosome number revealed that the three species have the same number of chromosomes: 2n=18. Parameters describing genetic diversity indicate a very low level of genetic variation of the studied populations. The isozyme data support hypothesis that strong directional selection can result in lower level of genetic variation of arid plant populations.

  12. Genetic structure of Rajaka caste and affinities with other caste populations of Andhra Pradesh, India.

    Science.gov (United States)

    Parvatheesam, C; Babu, B V; Babu, M C

    1997-01-01

    The present study gives an account of the genetic structure in terms of distribution of a few genetic markers, viz., A1A2B0, Rh(D), G6PD deficiency and haemoglobin among the Rajaka caste population of Andhra Pradesh, India. The genetic relationships of the Rajaka caste with other Andhra caste populations were investigated in terms of genetic distance, i.e., Sq B (mn) of Balakrishnan and Sanghvi. Relatively lesser distance was established between the Rajaka and two Panchama castes. Also, the pattern of genetic distance corroborates the hierarchical order of the Hindu varna system.

  13. Isozyme analysis of Taenia solium isolates from Mexico and Colombia.

    Science.gov (United States)

    Maravilla, Pablo; Valera, Aldo; Souza, Valeria; Martinez-Gordillo, Mario; Flisser, Ana

    2003-12-01

    Mexican and Colombian Taenia solium cysticerci and some species of Taenia adults were assayed using cellulose acetate electrophoresis to distinguish between isolates. Isozyme patterns for ARK, GOT, G3PD, GPI, and MPI were identical in all cysticerci suggesting homozygotic profiles. G6PD and MDH showed different patterns between Mexican and Colombian cysticerci, suggesting regional differences. ME activity was mainly detected in the adult stage suggesting that this enzyme is active in anaerobic environment, while MDH, detected in cysticerci, could be related to an environment that contains oxygen. Finally, the species of taeniid adults analyzed showed different patterns among them.

  14. Glusoce-6-phosphate dehydrogenase- History and diagnosis

    Directory of Open Access Journals (Sweden)

    K Gautam

    2016-09-01

    Full Text Available Glucose-6-phosphate dehydrogenase deficiency is the most common enzymatic defect of red blood cells, which increases the vulnerability of erythrocytes to oxidative stress leading to hemolytic anemia. Since its identification more than 60 years ago, much has been done with respect to its clinical diagnosis, laboratory diagnosis and treatment. Association of G6PD is not just limited to anti malarial drugs, but a vast number of other diseases. In this article, we aimed to review the history of Glucose-6-phosphate dehydrogenase, the diagnostic methods available along with its association with other noncommunicable diseases. 

  15. Frequency of Thalassemia, Iron and Glucose-6Phosphate Dehydrogenase Deficiency Among Turkish Migrating Nomad Children in Southern Iran

    Directory of Open Access Journals (Sweden)

    Mehrabani D

    2009-04-01

    Full Text Available Ferropenia and consequent iron deficiency anemia (IDA, β-thalassemia, and glucose 6-phosphate dehydrogenase (G6PD deficiency are three main common hematological problems in Iran. This study was conducted to investigate the prevalence of these problems in Turkish migrating nomads in southern Iran. From June to October 2006, the blood sample of 152 Turkish migrating nomadic children including 79 (52% males and 73 (48% females were evaluated for iron indices and G6PD deficiency in southern Iran. The family history of thalassemia, favism, and signs and symptoms related to anemia of participants were determined. RBC count, different types of Hb, Hct, MCV, MCH, MCHC, RDW, SI, TIBC and SF were measured immediately after blood sampling. Twenty-seven (17.7% children had serum ferritin (SF level <12 ng/dL, while this low serum ferritin level was similar in both genders. The low hemoglobin (Hb level had a statistical correlation with the low serum ferritin level. Among all participants, the prevalence of G6PD deficiency was 7.2% which was more frequent in males compared to females (8.9% vs. 5.5%. Seven (4.6% children had Hb  3.5 g/dL; and the prevalence of β-thalassemia trait was higher in female children compared with males (5.5% vs. 3.8%. The prevalence of IDA was 17.7%. Although this figure is less than the prevalence found in other developing countries (25-35%; but it shows that Turkish ethnic nomads in southern Iran are still behind the health statues in the industrialized countries (5-8%. The relatively high prevalence of β-thalassemia trait also is a major potential risk; and careful performance of Iranian thalassaemia program is highly suggested. It seems that G6PD deficiency is a prevalent disease in migrating Turkish nomads, and again establishment of educational programs, and investigation of dietary habits of Turkish migrating nomads on how and by whom the fava beans are consumed; seems to be a good way to prevent favism.

  16. [Aregenerative anemia and erythrocytes hemighosts: a case report].

    Science.gov (United States)

    Bibi-Triki, Tewfik; Bélien, Valérie; Chapelon, Emeline; Sauvion, Sylvie; Gaudelus, Joel; Laurian, Yves; de Pontual, Loïc

    2011-01-01

    An 11 year old African boy without previous history was hospitalised for fever and a severe anaemia (haemoglobin = 55 g/L) with low reticulocyte count. Blood smear showed more than 35% of ghost red blood cells which allows the diagnosis of G6PD deficiency (< 1% of normal level). Anaemia was demonstrated as haemolytic and was associated with a drepanocytosis trait. Aspect of red blood cells on blood smear remains important for the diagnosis of congenital or acquired red blood cell diseases, even abnormalities are often of low specificity.

  17. Dicty_cDB: SFG159 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 4e-12 2 D88434 |D88434.1 Malus domestica mRNA for protein abundantly expressed during apple fruit developm...ent, complete cds. 72 9e-09 1 AY034889 |AY034889.1 Tortula ruralis aldehyde dehydro

  18. Dicty_cDB: CFB743 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 4e-12 2 D88434 |D88434.1 Malus domestica mRNA for protein abundantly expressed during apple fruit developm...ent, complete cds. 72 1e-08 1 AY034889 |AY034889.1 Tortula ruralis aldehyde dehydro

  19. AcEST: DK960664 [AcEST

    Lifescience Database Archive (English)

    Full Text Available FM01|UGDH2_ARATH Probable UDP-glucose 6-dehydrogenase 2 OS=... 370 e-102 sp|Q9LIA8|UGDH1_ARATH Probable UDP-...+GKPLDPW+ Sbjct: 445 DGRNIMNVNKLREIGFIVYSIGKPLDPWL 473 >sp|Q9LIA8|UGDH1_ARATH Probable UDP-glucose 6-dehydro

  20. Arabidopsis CDS blastp result: AK061085 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061085 006-206-G01 At1g22410.1 2-dehydro-3-deoxyphosphoheptonate aldolase, putative / 3-deoxy-D-arab...ino-heptulosonate 7-phosphate synthase, putative / DAHP synthetase, putative similar to 3-deoxy-D-arab

  1. Arabidopsis CDS blastp result: AK059247 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059247 001-024-G06 At1g22410.1 2-dehydro-3-deoxyphosphoheptonate aldolase, putative / 3-deoxy-D-arab...ino-heptulosonate 7-phosphate synthase, putative / DAHP synthetase, putative similar to 3-deoxy-D-arab

  2. Arabidopsis CDS blastp result: AK069083 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069083 J023009C02 At1g22410.1 2-dehydro-3-deoxyphosphoheptonate aldolase, putative / 3-deoxy-D-arab...ino-heptulosonate 7-phosphate synthase, putative / DAHP synthetase, putative similar to 3-deoxy-D-arab

  3. Arabidopsis CDS blastp result: AK070359 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070359 J023054B06 At1g22410.1 2-dehydro-3-deoxyphosphoheptonate aldolase, putative / 3-deoxy-D-arab...ino-heptulosonate 7-phosphate synthase, putative / DAHP synthetase, putative similar to 3-deoxy-D-arab

  4. Arabidopsis CDS blastp result: AK069968 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069968 J023038D13 At1g22410.1 2-dehydro-3-deoxyphosphoheptonate aldolase, putative / 3-deoxy-D-arab...ino-heptulosonate 7-phosphate synthase, putative / DAHP synthetase, putative similar to 3-deoxy-D-arab

  5. Sequence Classification: 52362 [

    Lifescience Database Archive (English)

    Full Text Available TMB Non-TMH TMB TMB Non-TMB Non-TMB >gi|50083418|ref|YP_044928.1| 5-dehydro-4-deoxyglucar...ate dehydratase (5-keto-4-deoxy-glucarate dehydratase) || http://www.ncbi.nlm.nih.gov/protein/50083418 ...

  6. An in vitro comparison of the cytotoxic potential of selected dehydropyrrolizidine alkaloids and some N-oxides

    Science.gov (United States)

    Plants containing dehydro-pyrrolizidine alkaloids (PAs) can be found throughout the world and their invasive, weedy nature often results in PA contamination of feed and food. Other PA-containing plants may be purposefully or accidentally included in food or herbal preparations. Poisoning can be acu...

  7. Gclust Server: 21848 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 21848 Afu_AF1928=fwdD-2 Cluster Sequences - 122 tungsten formylmethanofuran dehydro...resentative annotation tungsten formylmethanofuran dehydrogenase, subunit D (fwdD...F1928=fwdD-2 Link to cluster sequences Cluster Sequences Link to related sequences - Sequence length 122 Rep

  8. Mass-array芯片技术在葡萄糖-6-磷酸脱氢酶基因突变位点检测中的应用%Application of Mass-array gene chip to detect glucose-6-phosphate dehydrogenase gene mutations

    Institute of Scientific and Technical Information of China (English)

    陈瑶; 苏跃青; 周进福; 王旌; 赵红; 曾颖琳; 林庆颖; 林枫; 张洪华

    2015-01-01

    目的 探讨应用Mass-array基因芯片技术检测葡萄糖-6-磷酸脱氢酶(G6PD)基因突变位点的价值,并对其进行质量评价.方法 收集2006至2013年在福建省妇幼保健院新生儿疾病筛查中心进行G6PD筛查的婴儿,根据化学筛查结果分成2组:G6PD缺乏症患儿和正常儿童,随机抽取患儿和正常对照儿童各300例.采用基因分析工具(Genotyping Tools)与Mass-array Design软件,利用中国人群已报道的G6PD基因33个突变位点芯片,应用Mass-array基因技术检测G6PD基因突变位点,并通过DNASanger测序法验证基因芯片检测结果的准确性.结果 在300例G6PD患儿中,共检出单纯型单点突变9种:1376G>T、1388G>A、95A>G、1024C>T、392G>T、1360C>T、487G>A、517T>C、1365-13T>C;复合突变型7种:871G> A/1365-13T> C/1311C>T、1004C> A/1311C> T/1365-13T>C、1376G >T/1365-13T>C/1311C>T、1365-13T >C/1311C >T、1376G> T/1365-13T>C、95A> G/1365-13T> C/1311C>T、1388G> A/1365-13T>C;300名正常对照儿童中未检测到G6PD基因突变.进一步所有样本的Sanger DNA测序结果与基因芯片检测结果完全一致.结论 采用Massarray基因芯片技术检测G6PD基因突变方法是一种准确、高效的G6PD基因突变筛查方法.%Objective To develop the Mass-array gene chip to detect glucose-6-phosphate dehydrogenase (G6PD) gene mutations,and to evaluate its quality.Methods Randomly choosing the children who perform neonatal screening in Neonatal Screening Center of Fujian Maternity and Children Health Hospital from 2006 to 2013.Children were divided into control group and G6PD patient group.Using Genotyping Tools from Sequenom company and the software of Mass-array Assay Design to design the PCR amplification primer of 33 G6PD gene mutations which were well-known in Chinese.Then depending on Mass-array gene chip technology to detect glucose-6-phosphate dehydrogenase gene mutations.DNA Sanger sequencing was

  9. Genotyping by"cold single-strand conformation polymorphism" of the UGT1A1 promoter polymorphism in Mexican mestizos.

    Science.gov (United States)

    Arámbula, Eliakym; Vaca, Gerardo

    2002-01-01

    Since no data have previously been reported concerning both the (TA) n polymorphism at the promoter of the UGT1A1 gene in the Mexican population and the use of single-strand conformation polymorphism (SSCP) for the detection of such polymorphism, genotyping by SSCP in 375 G-6-PD normal (Group A) and 81 G-6-PD-deficient (Group B) mestizos belonging to 14 states was carried out. Allele frequencies for (TA)6 and (TA)7 repeats were 0.654 and 0.334, respectively, in Group A and 0.685 and 0.315 in Group B; in the former group, the (TA)5 allele was also observed with a frequency of 0.012. The frequencies of the genotype (TA)7/(TA)7 were 10.1% (Group A) and 8.6% (Group B). The (TA)7/(TA)8 genotype was also observed in a patient with unconjugated hyperbilirubinemia. Due to the importance of its potential medical implications, the observed high frequency (10%) of the (TA)7/(TA)7 genotype is stressed. Genotyping by SSCP of the (TA) n polymorphism is an adequate methodological option.

  10. The efficiency of malaria chemoprophylaxis

    Directory of Open Access Journals (Sweden)

    Vasiliki Pappa

    2008-07-01

    Full Text Available Introduction: Malaria is a highly contagious disease. According to WHO, malaria cases are expected to increase due to climate changes. Despite the eradication efforts, malaria still remains one of the most significant causes of morbidity and mortality in tropical and subtropical regions. Many different antimalarial regimens are used , however resistance is emerging to many of themPurpose: This critical review was conducted, in order to respond to the following questions. A Which antimalarial regimen is most effective? B Which regimen is the safest for travelers in endemic regions? C Which regimen is best tolerated?Methodology: The literature research was conducted through the Internet. The Medline and Cinahl databases were used, as well as the search engines google, altavista and lycos. The research included articles that described clinical trials. The material was selected based on the aforementioned research questions and the chronological time limits.Results: Atovaquone/proguanil, tafenoquine, primaquine were the most effective regimens. Tafenoquine, as well as, primaquine have been related to hemolytic events in individuals with G6PD deficiency, gastrointestinal disorders, backache and flue-like syndrome. Doxycycline and mefloquine were related to gastrointestinal and neurological disorders. Those were the less tolerated regimens.Conclusions: Atovaquone/proguanil, tafenoquine, primaquine were the most effective regimens. As far as safety is concerned, tafenoquine and primaquine should not be prescribed to individuals with G6PD deficiency. All the regimens were considered well tolerated, however, in doxycycline and mefloquine trials were the most withdrawals due to adverse effects.

  11. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  12. Splenic artery pseudoaneurysm due to seatbelt injury in a glucose-6-phosphate dehydrogenase-deficient adult.

    Science.gov (United States)

    Lau, Yu Zhen; Lau, Yuk Fai; Lai, Kang Yiu; Lau, Chu Pak

    2013-11-01

    A 23-year-old man presented with abdominal pain after suffering blunt trauma caused by a seatbelt injury. His low platelet count of 137 × 10(9)/L was initially attributed to trauma and his underlying hypersplenism due to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Despite conservative management, his platelet count remained persistently reduced even after his haemoglobin and clotting abnormalities were stabilised. After a week, follow-up imaging revealed an incidental finding of a pseudoaneurysm (measuring 9 mm × 8 mm × 10 mm) adjacent to a splenic laceration. The pseudoaneurysm was successfully closed via transcatheter glue embolisation; 20% of the spleen was also embolised. A week later, the platelet count normalised, and the patient was subsequently discharged. This case highlights the pitfalls in the detection of a delayed occurrence of splenic artery pseudoaneurysm after blunt injury via routine delayed phase computed tomography. While splenomegaly in G6PD may be a predisposing factor for injury, a low platelet count should arouse suspicion of internal haemorrhage rather than hypersplenism.

  13. Neonatal hyperglycemia induces oxidative stress in the rat brain: the role of pentose phosphate pathway enzymes and NADPH oxidase.

    Science.gov (United States)

    Rosa, Andrea Pereira; Jacques, Carlos Eduardo Dias; de Souza, Laila Oliveira; Bitencourt, Fernanda; Mazzola, Priscila Nicolao; Coelho, Juliana Gonzales; Mescka, Caroline Paula; Dutra-Filho, Carlos Severo

    2015-05-01

    Recently, the consequences of diabetes on the central nervous system (CNS) have received great attention. However, the mechanisms by which hyperglycemia affects the central nervous system remain poorly understood. In addition, recent studies have shown that hyperglycemia induces oxidative damage in the adult rat brain. In this regard, no study has assessed oxidative stress as a possible mechanism that affects the brain normal function in neonatal hyperglycemic rats. Thus, the present study aimed to investigate whether neonatal hyperglycemia elicits oxidative stress in the brain of neonate rats subjected to a streptozotocin-induced neonatal hyperglycemia model (5-day-old rats). The activities of glucose-6-phosphate-dehydrogenase (G6PD), 6-phosphogluconate-dehydrogenase (6-PGD), NADPH oxidase (Nox), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), the production of superoxide anion, the thiobarbituric acid-reactive substances (TBA-RS), and the protein carbonyl content were measured. Neonatal hyperglycemic rats presented increased activities of G6PD, 6PGD, and Nox, which altogether may be responsible for the enhanced production of superoxide radical anion that was observed. The enhanced antioxidant enzyme activities (SOD, CAT, and GSHPx) that were observed in neonatal hyperglycemic rats, which may be caused by a rebound effect of oxidative stress, were not able to hinder the observed lipid peroxidation (TBA-RS) and protein damage in the brain. Consequently, these results suggest that oxidative stress could represent a mechanism that explains the harmful effects of neonatal hyperglycemia on the CNS.

  14. Inactivation of Bakers' yeast glucose-6-phosphate dehydrogenase by aluminum

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sungwoo; Joshi, J.G. (Univ. of Tennessee, Knoxville (USA))

    1989-04-18

    Preincubation of yeast glucose-6-phosphate dehydrogenase (G6PD) with Al(III) produced an inactive enzyme containing 1 mol of Al(III)/mol of enzyme subunit. None of the enzyme-bound Al(III) was dissociated by dialysis against 10 mM Tris-HCl, pH 7.0, containing 0.2 mM EDTA at 4{degree}C for 24 h. Citrate, NADP{sup +}, EDTA, or NaF protected the enzyme against the Al(III) inactivation. The Al(III)-inactivated enzyme, however, was completely reactivated only by citrate and NaF. The dissociation constant for the enzyme-aluminum complex was calculated to be 4 {times} 10{sup {minus}6} M with NaF, a known reversible chelator for aluminum. Modification of histidine and lysine residues of the enzyme with diethyl pyrocarbonate and acetylsalicylic acid, respectively, inactivated the enzyme. However, the modified enzyme still bound 1 mol of Al(III)/mol of enzyme subunit. Circular dichroism studies showed that the binding of Al(III) to the enzyme induced a decrease in {alpha}-helix and {beta}-sheet and an increase in random coil. Therefore, it is suggested that inactivation of G6PD by Al(III) is due to the conformational change induced by Al(III) binding.

  15. An unexpected emergency request for glucose-6-phosphate dehydrogenase testing in a 9-year-old African American boy.

    Science.gov (United States)

    Platteborze, Peter; Matos, Renee; Gidvany-Diaz, Vinod; Wilhelms, Kelly

    2015-01-01

    9-year-old African American male. Recently diagnosed with acute lymphoblastic leukemia (ALL) after investigation into a large anterior mediastinal mass causing airway compression. The day before the unexpected urgent glucose-6-phosphate dehydrogenase (G6PD) request, the patient was diagnosed with an aggressive form of leukemia and a significant tumor mass causing airway compression. A computed tomography (CT) scan indicated potential renal involvement. Based on this information and the size of the mass, the patient was referred for immediate chemotherapy. However, there was a concern that he could develop tumor lysis syndrome (TLS) during treatment. To avoid this condition, the pediatric intensive care unit (ICU) sought to pretreat the child with rasburicase, which led to the emergency G6PD request. Unknown. Largely unknown, but no apparent chronic diseases. Three weeks of progressively worsening lymphadenopathy, coughing, night sweats, mild hepatosplenomegaly, and breathing difficulty when supine. The patient arrived at the medical center for airway management and had a temperature of 36.1°C; blood pressure, 120/87 mmHg; pulse, 115 bpm; respiratory rate, 22 breaths per minute, with labored breathing but normal O(2) saturation while upright and awake, in room air. Table 1. Copyright© by the American Society for Clinical Pathology (ASCP).

  16. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    Energy Technology Data Exchange (ETDEWEB)

    Finan, A.; Cleary, M.P.

    1986-03-05

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either (1-/sup 14/C) glucose or (6-/sup 14/C) glucose resulted in significant decreases in CO/sub 2/ production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats.

  17. Identification of novel RFLPs in the vicinity of CpG islands in Xq28: application to the analysis of the pattern of X chromosome inactivation.

    Science.gov (United States)

    Maestrini, E; Rivella, S; Tribioli, C; Rocchi, M; Camerino, G; Santachiara-Benerecetti, S; Parolini, O; Notarangelo, L D; Toniolo, D

    1992-01-01

    Probes for CpG islands were cloned from the distal long arm of the human X chromosome; three of them were found to be polymorphic. A HindIII RFLP was identified by the probe 2-25 (DXS606), and it was mapped to the Xq27-Xq28 boundary. Probes 2-19 (DXS605) and 2-55 (DXS707), which identify EcoRI and MspI polymorphisms, respectively, have been mapped to the distal part of Xq28, in the G6PD-RCP/GCP gene region. Probe 2-19 has been further localized about 16 kb from the 3' end of the G6PD gene. The new RFLPs may be useful for the precise mapping of the many disease genes localized in this part of the human X chromosome. Probe 2-19 is highly informative, and it has been studied in greater detail. Using the methylation-sensitive rare-cutter enzyme EagI in conjunction with the polymorphic EcoRI site, we were able to demonstrate that the RFLP may be used both to study randomness of X chromosome inactivation and for carrier detection in X-linked syndromes where nonrandom X inactivation occurs. It is conceivable that the combined use of 2-19 and of the probes described so far (pSPT-PGK and M27 beta) will make analysis of X inactivation feasible in virtually every female.

  18. Identification of novel RFLPs in the vicinity of CpG islands in Xq28: Application to the analysis of the pattern of X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Camerino, G.; Santachiara-Benerecetti, S. (Univ. di Pavia (Italy)); Rocchi, M. (Univ. di Bari (Italy)); Parolini, O.; Notarangelo, L.D. (Univ. di Brecscia (Italy)); Maestrini, E.; Rivella, S.; Tribioli, C.; Toniolo, D.

    1992-01-01

    Probes of CpG islands were cloned from the distal long arm of the human X chromosome; three of them were found to be polymorphic. A HindIII RFLP was identified by the probe 2-25 (DXS606), and it was mapped to the Xq27-Xq28 boundary. Probes 2-19 (DXS605) and 2-55 (DXS707), which identify EcoRI and MspI polymorphisms, respectively, have been mapped to the distal part of Xq28, in the G6PD-RCP/GCP gene region. Probe 2-19 has been further localized about 16 kb from the 3{prime} end of the G6PD gene. The new RFLPs may be useful for the precise mapping of the many disease genes localized in this part of the human X chromosome. Using the methylation-sensitive rare-cutter enzyme EagI in conjunction with the polymorphic EcoRI site, the authors were able to demonstrate that the RFLP may be used both to study randomness of X chromosome inactivation and for carrier detection in X-linked syndromes where nonrandom X inactivation occurs. It is conceivable that the combined use of 2-19 and of the probes described so far (pSPT-PGK and M27{beta}) will make analysis of X inactivation feasible in virtually every female.

  19. Oxidative Stress in Patients With Nongenital Warts

    Directory of Open Access Journals (Sweden)

    Sezai Sasmaz

    2005-01-01

    Full Text Available Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT, glucose-6-phosphate dehydrogenase (G6PD, superoxide dismutase (SOD, and malondialdehyde (MDA in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (P<.05. However, we could not define a statistically significant correlation between these increased enzyme activities and MDA levels and the type, the duration, the number, and the location of lesions. We determined possible suppression of T cells during oxidative stress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

  20. [Erythrocyte polymorphism in Mali: epidemiology and resistance mechanisms against severe Plasmodium falciparum malaria].

    Science.gov (United States)

    Doumbo, Ogobara

    2007-01-01

    Homo sapiens and Plasmodium falciparum have co-evolved since the beginning of agriculture, 10,000 to 20,000 years ago. By domesticating plants and animals, humans linked their destiny to one of the main vectors of malaria, Anopheles gambiae sl complex. The biological interaction between these three species led to exchanges of genes and biochemical processes with significant mutual influence. Humans acquired mutations with selective protective advantages against serious and fatal forms of this hemosporidiosis. This is the case of hemoglobin S, hemoglobin C, hemoglobin E, thalassemias, ovalocytosis and G6PD deficiency, among others. Many epidemiological studies published since 1949 have shown a geographic link between malaria and certain erythrocyte polymorphisms. The link with hemoglobin C was discovered only recently, in 2000, initially in Mali in the Dogon population, then in Burkina Faso. Epidemiological and molecular and cellular biology studies done in Mali and elsewhere showed that the C and S alleles, and G6PD deficiency [A-], conferred significant protection against lethal forms of Plasmodium falciparum malaria. Molecular genetic studies, based on functional genomics, transcriptomics and proteomics, provided possible explanations. Advances in molecular biology and a better understanding of the immune mechanisms underlying this protection will hopefully lead to the development of effective second- and third-generation malaria vaccines. Epidemiological and fundamental research efforts have identified some of the mechanisms by which these erythrocyte polymorphisms protect against the most lethal hematozoan parasite, Plasmodium falciparum.

  1. Aczone, a topical gel formulation of the antibacterial, anti-inflammatory dapsone for the treatment of acne.

    Science.gov (United States)

    Scheinfeld, Noah

    2009-05-01

    Allergen Inc has launched Aczone, a topical gel formulation of the antibacterial, anti-inflammatory agent dapsone, for the potential treatment of acne vulgaris. Oral dapsone has demonstrated efficacy in acne, but was associated with severe side effects such as anemia, which was particularly serious in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Aczone was developed to overcome this limitation, and is formulated using solvent-microparticle technology for improved absorption and action and for fewer side effects. In a phase I clinical trial, systemic exposure to dapsone was 126-fold lower following treatment with Aczone compared with oral dapsone. Aczone significantly reduced lesion counts in patients with acne in phase III trials, and was particularly effective in reducing inflammatory lesions. In a phase IV trial, Aczone was safely applied to patients with G6PD deficiency without inducing anemia. Phase IV trials in patients with acne were ongoing at the time of publication to assess safety and to compare Aczone monotherapy with combinations of Aczone and other anti-acne therapeutics. At the time of publication, Allergen was also developing Aczone for the treatment of rosacea; the drug was undergoing phase II trials for this indication. Aczone appears to be a novel promising anti-acne therapeutic option, particularly for patients with inflammatory acne.

  2. Epidemiology of hyperbilirubinemia in the first 24 hours after birth

    Directory of Open Access Journals (Sweden)

    Zarrinkoub F

    2007-09-01

    Full Text Available   Background: Jaundice is one of the most frequent problems observed in newborns. Our purpose was to investigate the incidence and the risk factors on jaundice noted in the first 24 hours after birth.Methods: All newborns observed to have jaundice within the first 24 hours after birth were enrolled prospectively in this study. Laboratory evaluations included blood group typing of mother and newborn, hemoglobin and hematocrit, complete blood count, peripheral blood smear, reticulocyte count, G6PD activity, maternal indirect and neonatal direct Coombs test, and serum total, conjugated, and unconjugated bilirubin. In all cases, gender, birth weight, Apgar scores, gestational age, mode of delivery, birth trauma, cephalhematoma, maternal age, parity, or any siblings with neonatal jaundice were recorded. Data were analyzed using one-way ANOVA, Student's t-, and chi-square tests.Results: Of a total of 2096 newborns delivered in one year, 122 (5.8% developed jaundice within the first 24 hours after birth. Risk factors for hyperbilirubinemia were ABO incompatibility, prematurity, infection, G6PD deficiency, cephalhematoma, asphyxia, and Rh disease. There were no statistically significant relationships between jaundice and maternal age, parity, mode of delivery, neonatal gender or previous siblings with jaundice (p>0.05.Conclusions: Jaundice observed in the initial 24 hours after birth was infrequent, but clinically significant. All newborns should be followed by repeated exams within the first 24 hours after birth and before discharge, especially if the maternal blood group is O.

  3. Increase of energy balance significantly alters major lipogenic gene expression in lactation ewes.

    Science.gov (United States)

    Laliotis, George P; Bizelis, Iosif; Vitsa, Alkistis; Rogdakis, Emmanuel

    2012-01-01

    The objective of the present study was to examine changes observed in the expression of cytosolic NADP isocitrate dehydrogenase (ICDH) and glucose 6-phosphate dehydrogenase (G6PD) genes, the major implicated genes in ruminant lipogenesis in terms of produce NADPH, during the early post-weaning period in dairy ewes in respect to energy intake, and to further correlate the noted changes with their respective enzymatic activities. A total of 21 subcutaneous adipose tissue samples were obtained from seven lactating (2nd lactation period) dairy ewes of the Chios breed. Adipose tissue samples were taken from the tail head region at weeks 1, 2, and 4 after weaning (45 days after parturition). Dairy ewes were in negative energy balance during weeks 1 and 2 after weaning and they moved into a strong positive energy balance at week 4 after weaning. Expression of ICDH and G6PD genes and their respective enzymatic activity was determined. Results showed that both genes' expression and enzymatic activities were significantly minimal at week 1 after weaning, reaching a maximum level at week 4 after weaning (P gene expression (P energy intake changes. Almost similar changes were observed for enzymatic activities, rendering these enzymes as potential biochemical markers of ovine lipogenesis. Copyright © Taylor & Francis Group, LLC

  4. Randomized, parallel placebo-controlled trial of primaquine for malaria prophylaxis in Papua, Indonesia.

    Science.gov (United States)

    Baird, J K; Lacy, M D; Basri, H; Barcus, M J; Maguire, J D; Bangs, M J; Gramzinski, R; Sismadi, P; Krisin; Ling, J; Wiady, I; Kusumaningsih, M; Jones, T R; Fryauff, D J; Hoffman, S L

    2001-12-15

    Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attacking liver-stage parasites, a property distinguishing it from most chemoprophylactics and obviating 4-week postexposure dosing. A daily adult regimen of 30 mg primaquine prevented malaria caused by Plasmodium falciparum and P. vivax for 20 weeks in 95 of 97 glucose-6-phosphate dehydrogenase (G6PD)-normal Javanese transmigrants in Papua, Indonesia. In comparison, 37 of 149 subjects taking placebo in a parallel trial became parasitemic. The protective efficacy of primaquine against malaria was 93% (95% confidence interval [CI] 71%-98%); against P. falciparum it was 88% (95% CI 48%-97%), and >92% for P. vivax (95% CI >37%-99%). Primaquine was as well tolerated as placebo. Mild methemoglobinemia (mean of 3.4%) returned to normal within 2 weeks. Blood chemistry and hematological parameters revealed no evidence of toxicity. Good safety, tolerance, and efficacy, along with key advantages in dosing requirements, make primaquine an excellent drug for preventing malaria in nonpregnant, G6PD-normal travelers.

  5. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure.

    Science.gov (United States)

    Díaz-Flores, Margarita; Cruz, Miguel; Duran-Reyes, Genoveva; Munguia-Miranda, Catarina; Loza-Rodríguez, Hilda; Pulido-Casas, Evelyn; Torres-Ramírez, Nayeli; Gaja-Rodriguez, Olga; Kumate, Jesus; Baiza-Gutman, Luis Arturo; Hernández-Saavedra, Daniel

    2013-10-01

    Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months. We analysed thiobarbituric acid reactive substances (TBARS) and S-nitrosohemoglobin (SNO-Hb) in plasma; the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in erythrocytes; and the expression of CAT, GPX, and SOD2 in leukocytes. Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group. Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043). Glycine plays an important role in balancing the redox reactions in the human body, thus protecting against oxidative damage in MetS patients.

  6. The high incidence of acute hemolysis due to favism in Ahvaz, Iran-clinical features and laboratory findings

    Institute of Scientific and Technical Information of China (English)

    Seyyed Mohammad Hasan Aletayeb; Bashir Chomeili; Mehri Taheri; Tahereh Ziaei Kajbaf; Mehran Hakimzadeh; Majid Aminzadeh; Morteza Shojaei Moghadam; Susan Maleki

    2010-01-01

    Objective:To collect comprehensive information about the features of favic patients in Ahvaz (Capital of Khouzestan, Iran) and analyze the extent of the differences with their corresponding in other regions. Methods:A total of 103 patients with acute hemolysis admitted to pediatric division of Abouzar Hospital located in the city of Ahvaz, Iran during 21st of June 2008 to 20th of June 2009 were analyzed retrospectively. Results:95.14%of the patients had favism while 4.86%of them underwent hemolysis due to other reasons. These patients were male (68.93%) and female children (31.06%) admitted mostly during the spring season. The three main symptoms were urine discoloration, jaundice and vomiting. At the admission time, the main hematologic findings were as follows:G6PD sufficient status (45.63%), G6PD deficient status (54.36%) and hemoglobin concentration:2.5-11.8 (mean±SD:6.45±2.12) g/dL. Conclusions:In conclusion, Ahvaz was determined as a black zone for favism in which the disease can be considered a life threatening health problem. Moreover, slight differences were observed in the three main symptoms compared with favic patients in other regions.

  7. Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate dehydrogenase deficiency among Arab migrating nomad children, southern Islamic Republic of Iran.

    Science.gov (United States)

    Pasalar, M; Mehrabani, D; Afrasiabi, A; Mehravar, Z; Reyhani, I; Hamidi, R; Karimi, M

    2014-12-17

    This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and β-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating β-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of β-thalassaemia trait was the major potential risk factor in this population.

  8. Ultrastructural and Biochemical Evaluation of the Effect of Endosulfan on Mice Liver

    Directory of Open Access Journals (Sweden)

    Yildiz Caglar

    2013-04-01

    Full Text Available Purpose: The aim of this study is to examine the effect of endosulfan on mice liver as ultrastructural together with biochemical data, and also by light microscopy to evaluate. Materials and Methods: 12 male albino mice weighing between 26-30g were used. Mice were divided into two equal groups. For group receiving endosulfan, endosulfan (13 mg/kg/day, body weight dissolved in nut oil was administered orally to mice via intragastric-during 10 days. The control group received only nut oil. At the end of the 10th day, all the mice were sacrificed with cervical dislocation. Tissue samples were taken for histological examination and biochemical analysis (SOD; superoxide dismutase, GSH; glutathione peroxidase, CAT; catalase, G6PD; glucose-6-phosphate dehidrogenase, MDA; malondialdehyde. Results: Disruption of inner membrane of mitochondria, dilatation of endoplasmic reticulum, the presence of large lipid droplets and vacuolar structures were observed in some hepatocytes. Prominent vacuolization was seen in light microscopic observation. There was an increment in activities of G6PD, SOD, GSH and MDA. However, there was a decrease in CAT activity. Conclusion: It may be considered that the adverse effect of endosulfan on mice liver may be due to direct toxic effect of endosulfan and induction of oxidative stress. [Cukurova Med J 2013; 38(2.000: 274-284

  9. Epidemiology of Plasmodium vivax in Indonesia.

    Science.gov (United States)

    Surjadjaja, Claudia; Surya, Asik; Baird, J Kevin

    2016-12-28

    Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. © The American Society of Tropical Medicine and Hygiene.

  10. 广东省惠州市新生儿疾病筛查干预策略及实施效果分析%Neonatal screening intervention strategies and effect analysis of Huizhou City

    Institute of Scientific and Technical Information of China (English)

    潘文静

    2010-01-01

    Objective To investigate the screening of neonatal congenital hypothyroidism( CH) ,phenylketo-nuria(PKU) ,glucose -6 - phosphate dehydrogenase deficiency(G-6-PD) for need and the feasibility,building methods and intervention strategies for early detection,early diagnosis and early treatment of congenital metabolic diseases. Methods In 119 847 cases with neonatal congenital diseases, screening coverage was 71. 3% , the establishment of the city's leading group for neonatal screening and technical steering group,establish and improve neonatal screening network and the implementation of standardized management, improve the quality of neonatal screening, neonatal screening and intervention in the results were analyzed. Results In 119 847 cases,confirmed of CH 40 cases,the incidence rate was 0.03% ,PKU 2 cases,the incidence rate was 0.0017% ; G-6-PD 4326 cases, incidence rate was 3.60%. The incidence of G-6-PD was significantly higher than CH, PKU ( χ~2= 8.45, P <0.05); tracking rate was 91.6% ,the positive recall rate was 76. 8% ;42 children with timely treatment,avoiding the occurrence of mental retardation. Conclusion Three kinds of congenital disease prevention was effective, the need for further work to carry out neonatal screening coverage .particularly in rural areas, will be included in neonatal screening to the new rural cooperative medical coverage and improving the quality of newborn babies in Huizhou City.%目的 探讨开展新生儿先天性甲状腺功能减低症(CH)、苯丙酮尿症(PKU)、葡萄糖-6-磷酸脱氢酶缺乏症(G-6-PD)筛查的必要性和可行性,构建一套能早期发现、早期诊断、早期治疗先天性代谢性疾病的方法和干预策略.方法 对广东省惠州市119 847例新生儿进行先天性疾病筛查,筛查覆盖率为71.3%, 成立新生儿疾病筛查领导小组及技术指导小组,建立健全新生儿疾病筛查网络及实行标准化管理,并对新生儿疾病筛查干预

  11. MODELO TEÓRICO PARA EXPLICAR LA ACUMULACIÓN DE GOTAS LIPÍDICAS EN EMBRIONES BOVINOS MACHOS O HEMBRAS PRODUCIDOS in vitro Theoretical Model For Explaining Accumulation Of Fat Drops In In Vitro Produced Bovine Embryos

    Directory of Open Access Journals (Sweden)

    OMAR CAMARGO

    Full Text Available La glucosa 6-fosfato deshidrogenasa (G6PD, codificada por un gen ubicado en el cromosoma X, es la enzima limitante de vía de las pentosas fosfato (PF. La entrada de la glucosa así como su flujo y el rendimiento metabólico de esta vía están determinados tanto por los mismos niveles glucosa así como por la actividad de la G6PD. Por esta vía, la glucosa regula la trascripción de varios genes lipogénicos. En algunos embriones hembra producidos in vitro, se registra un retardo en la normal inactivación de uno de sus cromosomas X, lo cual se traduce en una doble actividad de los genes allí ubicados, si se compara con los embriones macho producidos in vitro. Se postula entonces que, la sobre-regulación de la vía PF a consecuencia de la doble dosis de su enzima limitante (G6PD y en presencia de elevados niveles de glucosa (mayores a 2,5 mM en el medio de cultivo, conllevaría a un dimorfismo sexual en relación con la transcripción de los genes Acetil CoA Carboxilasa Alfa (en adelante ACACA, símbolo oficial de la acetyl-Coenzyme A carboxylase alpha, y la Sintetasa de Ácidos Grasos (en edelante FASN, símbolo oficial de la fatty acid synthase que corriente abajo codifican para las enzimas limitantes en la síntesis de lípidos. Este dimorfismo sexual para el fenotipo metabolismo de lípidos, derivaría en una mayor acumulación citoplasmática de gotas lipídicas en los embriones hembra en comparación con los embriones machos que, de ser así, tendría efectos expansivos sobre el metabolismo general, la actividad transcripcional de otros genes y sobre la resistencia a la criopreservación.The encoding gene for glucose 6-phosphate dehydrogenase (G6PD is located on chromosome X. This enzyme regulates the entrance of glucose into the pentose phosphate pathway (PPP. Besides, throughout this route, glucose regulates the transcription of some lipogenic genes. Compared with in vitro produced male embryos, and due to a delaying in X

  12. Glucose-6-phosphate dehydrogenase and glutathione reductase activity in methemoglobin reduction by methylene blue and cyst amine: study on glucose-6-phosphate dehydrogenase-deficient individuals, on normal subjects and on riboflavin-treated subjects

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    Benedito Barraviera

    1988-10-01

    Full Text Available The authors have standardized methods for evaluation of the activity of the glucose-6-phosphate dehydrogenase and of glutathione reductase. The general principle of the first method was based on methemoglobin formation by sodium nitrite followed by stimulation of the glucose-6-phosphate dehydrogenase with methylene blue. Forty six adults (23 males and 23 females were studied. Subjects were not G6PD deficient and were aged 20 to 30 years. The results showed that methemoglobin reduction by methylene blue was 154.40 and 139.90 mg/min (p<0.05 for males and females, respectively, in whole blood, and 221.10 and 207.85 mg/min (n.s., respectively, in washed red cells. These data showed that using washed red cells and 0.7g% sodium nitrite concentration produced no differences between sexes and also shortened reading time for the residual amount of methemoglobin to 90 minutes. Glutathione reductase activity was evaluated on the basis of the fact that cystamine (a thiol agent binds to the SH groups of hemoglobin, forming complexes. These complexes are reversed by the action of glutathione reductase, with methemoglobin reduction occurring simultaneously with this reaction. Thirty two adults (16 males and 16 females were studied. Subjects were not G6PD deficient and were aged 20 to 30 years. Methemoglobin reduction by cystamine was 81.27 and 91.13 mg/min (p<0.01 for males and females, respectively. These data showed that using washed red cells and 0.1 M cystamine concentration permits a reading of the residual amount of methemoglobin at 180 minutes of incubation. Glutathione reductase activity was evaluated by methemoglobin reduction by cystamine in 14 females before and after treatment with 10 mg riboflavin per day for 8 days. The results were 73.69 and 94.26 jug/min (p<0.01 before and after treatment, showing that riboflavin treatment increase glutathione reductase activity even in normal individuals. Three Black G6PD-deficient individuals (2 males and 1

  13. Drug: D00118 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available genase-1 (COX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibit...proxen D00118 Naproxen (JP16/USP/INN) Target-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase...-1 (COX-1) [HSA:5742] [KO:K00509] Naproxen [ATC:G02CC02 M01AE02 M02AA12] D00118 Naproxen (JP16/USP/INN) cyclooxygen...8.gif Anti-inflammatory; Analgesic; Antipyretic Same as: C01517 Therapeutic category: 1149 ATC code: G02CC02 M01AE02 M02AA12 cyclooxy...ase-2 (COX-2) [HSA:5743] [KO:K11987] Naproxen [ATC:G02CC

  14. A quantitative cytochemical study of glucose-6-phosphate dehydrogenase and delta 5-3 beta-hydroxysteroid dehydrogenase activity in the membrana granulosa of the ovulable type of follicle of the rat.

    Science.gov (United States)

    Zoller, L C; Weisz, J

    1979-08-01

    During the last four days of follicular development prior to ovulation, the activities of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta OHD) and glucose-6-phosphate dehydrogenase (G-6-PD) were quantified in cryostat sections of the rat ovary. The product of the enzyme reactions were measured using a scanning and integrating microdensitometer. The enzyme activity was measured in the peripheral region, the antral region and the cumulus of the membrana granulosa (MG) of these follicles on the morning of each of the four days of the estrous cycle. G-6-PD activity was measured in the presence and absence of an intermediate hydrogen acceptor, phenazine methosulphate, to provide a measure of the quantity of Type I and Type II Hydrogen (H) generated: Type I H is considered to be related to hydroxylating reactions such as those of steroids and Type II H to other general biosynthetic activities of cells. In all three regions of the MG of follicles of the ovulable type, 3 beta OHD activity was lowest in estrus and diestrus-1, increased on diestrus-2 and peaked in proestrus. In estrus and diestrus-1, the level of 3 beta OHD activity in the three regions was comparable. However, by diestrus-2, and even more conspicuously in proestrus, enzyme activity was significantly greater in the peripheral region than in the antral region or in the cumulus. During the same period, the level of enzyme activity remained comparable in the last two regions. Throughout the estrous cycle, both Type I and Type II H generation from G-6-PD was greatest in the peripheral region, less in the antral region and least in the cumulus. In the eripheral region, Type I H generation increased progressively after diestrus-1, to reach a maximum in prestrus. In the antral region, Type I H generation increased between diestrus-1 and diestrus-2 and then remained unchanged through proestrus. In the cumulus, Type I H generation remained at levels seen in estrus throughout the remainder of the cycle. Generation

  15. MODELO TEÓRICO PARA EXPLICAR LA ACUMULACIÓN DE GOTAS LIPÍDICAS EN EMBRIONES BOVINOS MACHOS O HEMBRAS PRODUCIDOS in vitro

    Directory of Open Access Journals (Sweden)

    OLIVERA MARTHA

    2008-08-01

    Full Text Available La glucosa 6-fosfato deshidrogenasa (G6PD, codificada por un gen ubicado en el cromosoma X, es la enzima limitante de vía de las pentosas fosfato (PF. La entrada de la glucosa así como su flujo y el rendimiento metabólico de esta vía están determinados tanto por los mismos niveles glucosa así como por la actividad de la G6PD. Por esta vía, la glucosa regula la trascripción de varios genes lipogénicos. En algunos embriones hembra producidos in vitro, se registra un retardo en la normal inactivación de uno de sus cromosomas X, lo cual se traduce en una doble actividad de los genes allí ubicados, si se compara con los embriones macho producidos in vitro. Se postula entonces que, la sobre-regulación de la vía PF a consecuencia de la doble dosis de su enzima limitante (G6PD y en presencia de elevados niveles de glucosa (mayores a 2,5 mM en el medio de cultivo, conllevaría a un dimorfismo sexual en relación con la transcripción de los genes Acetil CoA Carboxilasa Alfa (en adelante ACACA, símbolo oficial de la acetyl-Coenzyme A carboxylase alpha, y la Sintetasa de Ácidos Grasos (en edelante FASN, símbolo oficial de la fatty acid synthase que corriente abajo codifican para las enzimas limitantes en la síntesis de lípidos. Este dimorfismo sexual para el fenotipo metabolismo de lípidos, derivaría en una mayor acumulación citoplasmática de gotas lipídicas en los embriones hembra en comparación con los embriones machos que, de ser así, tendría efectos expansivos sobre el metabolismo general, la actividad transcripcional de otros genes y sobre la resistencia a la criopreservación.

  16. MODELO TEÓRICO PARA EXPLICAR LA ACUMULACIÓN DE GOTAS LIPÍDICAS EN EMBRIONES BOVINOS MACHOS O HEMBRAS PRODUCIDOS in vitro

    Directory of Open Access Journals (Sweden)

    OMAR CAMARGO

    2008-01-01

    Full Text Available La glucosa 6-fosfato deshidrogenasa (G6PD, codificada por un gen ubicado en el cromosoma X, es la enzima limitante de vía de las pentosas fosfato (PF. La entrada de la glucosa así como su flujo y el rendimiento metabólico de esta vía están deter- minados tanto por los mismos niveles glucosa así como por la actividad de la G6PD. Por esta vía, la glucosa regula la trascripción de varios genes lipogénicos. En algunos embriones hembra producidos in vitro, se registra un retardo en la normal inactivación de uno de sus cromosomas X, lo cual se traduce en una doble actividad de los genes allí ubicados, si se compara con los embriones macho producidos in vitro. Se postula entonces que, la sobre-regulación de la vía PF a consecuencia de la doble dosis de su enzima limitante (G6PD y en presencia de elevados niveles de glucosa (mayores a 2,5 mM en el medio de cultivo, conllevaría a un dimorfismo sexual en relación con la transcripción de los genes Acetil CoA Carboxilasa Alfa (en adelante ACACA, símbolo oficial de la acetyl-Coenzyme A carboxylase alpha, y la Sintetasa de Ácidos Grasos (en edelante FASN, símbolo oficial de la fatty acid synthase que corriente abajo codifican para las enzimas limitantes en la síntesis de lípidos. Este dimorfismo sexual para el fenotipo metabolismo de lípidos, derivaría en una mayor acumulación citoplasmática de gotas lipídicas en los embriones hembra en comparación con los embriones machos que, de ser así, tendría efectos expansivos sobre el metabolismo general, la actividad transcripcional de otros genes y sobre la resistencia a la criopreservación.

  17. Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Zul Premji

    Full Text Available BACKGROUND: Chlorproguanil-dapsone-artesunate (CDA was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether-lumefantrine (AL efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD -deficient patients. METHODS AND FINDINGS: The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (> or =1 to <15 years old, median age 3 years with acute uncomplicated P. falciparum malaria were randomized (2:1 to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914 or six-doses of AL over three days (N = 458. Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP population using parasitological cure (polymerase chain reaction [PCR]-corrected. Cure rates were 94.1% (703/747 for CDA and 97.4% (369/379 for AL (treatment difference -3.3%, 95%CI -5.6, -0.9. CDA was non-inferior to AL, but there was simultaneous superiority of AL (upper 95%CI limit <0. Adequate clinical and parasitological response at Day 28 (uncorrected for reinfection was 79% (604/765 with CDA and 83% (315/381 with AL. In patients with a G6PD-deficient genotype (94/603 [16%] hemizygous males, 22/598 [4%] homozygous females, CDA had the propensity to cause severe and clinically concerning hemoglobin decreases: the mean hemoglobin nadir was 75 g/L (95%CI 71, 79 at Day 7 versus 97 g/L (95%CI 91, 102 for AL. There were three deaths, unrelated to study medication (two with CDA, one with AL. CONCLUSIONS: Although parasitologically effective at Day 28, the hemolytic potential of CDA in G6PD-deficient patients makes it unsuitable for use in a public health setting in Africa. TRIAL REGISTRATION: ClinicalTrials.Gov NCT

  18. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  19. Protective effects of the antioxidant Ginkgo biloba extract and the protease inhibitor aprotinin against Leiurus quinquestriatus venom-induced tissue damage in rats

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    A. J. Fatani

    2006-04-01

    Full Text Available Oxidative stress and proteases have been implicated in several diseases and extensive evidence indicates that antioxidants and protease inhibitors help prevent organ functional damage. Leiurus quinquestriatus (LQQ scorpion venom causes cellular injuries that may lead to multiple organ failure. Thus, the capability of the antioxidant "natural standardized extract of Gingko biloba leaves (Gin, EGb 761" and the non-selective protease inhibitor, aprotinin, in ameliorating venom-induced biochemical alterations indicative of cellular injury and oxidative stress was studied to determine their effectiveness in protecting rats from venom-evoked cellular damages. Thus, in this study, rats were treated with LQQ venom (0.3mg.kg-1, subcutaneously alone or after Gin (150mg.kg-1, orally, daily for 2 weeks before venom and/or aprotinin (Apr, 46000 KIU.kg-1, intraperitoneally, 30 min before venom. Control groups were injected with saline or treatment modalities. Lungs and hearts were excised after decapitating rats (n=8/group 60 min after venom injection and the following activities were measured: reduced glutathione (GSH, malondialdehyde (MDA - an index of lipid peroxidation, glutathione peroxidase (GPx, glucose-6-phosphate dehydrogenase (G6PD, and lactate dehydrogenase (LDH. Our findings demonstrate that LQQ venomsignificantly elevated GSH (p<0.05 vs. control, MDA (p<0.05, G6PD (p<0.05, and LDH activities (p<0.001 in hearts of envenomed rats. The venom also elevated MDA (p<0.05 vs. control and reduced GSH and GPx (p<0.05 in the lungs of envenomed rats. In general, pretreatment with EGb761 attenuated LQQ venom-evoked increases in GSH (p<0.05 vs. venom, MDA in rat hearts and lungs (p<0.05 vs. venom, plus LDH in the heart (p<0.01. Aprotinin alone significantly reduced the venom-elicited increase in G6PD and LDH activities and the decrease in GPx levels (p<0.05. In general, these protective effects of EGb761 on GSH, MDA (p<0.01 vs. venom and LDH (p<0.001 in the

  20. Progress towards malaria elimination in Sabang Municipality, Aceh, Indonesia

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    Herdiana Herdiana

    2013-01-01

    Full Text Available Abstract Background Indonesia has set 2030 as its deadline for elimination of malaria transmission in the archipelago, with regional deadlines established according to present levels of malaria endemicity and strength of health infrastructure. The Municipality of Sabang which historically had one of the highest levels of malaria in Aceh province aims to achieve elimination by the end of 2013. Method From 2008 to 2010, baseline surveys of malaria interventions, mapping of all confirmed malaria cases, categorization of residual foci of malaria transmission and vector surveys were conducted in Sabang, Aceh, a pilot district for malaria elimination in Indonesia. To inform future elimination efforts, mass screening from the focal areas to measure prevalence of malaria with both microscopy and PCR was conducted. G6PD deficiency prevalence was also measured. Result Despite its small size, a diverse mixture of potential malaria vectors were documented in Sabang, including Anopheles sundaicus, Anopheles minimus, Anopheles aconitus and Anopheles dirus. Over a two-year span, the number of sub-villages with ongoing malaria transmission reduced from 61 to 43. Coverage of malaria diagnosis and treatment, IRS, and LLINs was over 80%. Screening of 16,229 residents detected 19 positive people, for a point prevalence of 0.12%. Of the 19 positive cases, three symptomatic infections and five asymptomatic infections were detected with microscopy and 11 asymptomatic infections were detected with PCR. Of the 19 cases, seven were infected with Plasmodium falciparum, 11 were infected with Plasmodium vivax, and one subject was infected with both species. Analysis of the 937 blood samples for G6PD deficiency revealed two subjects (0.2% with deficient G6PD. Discussion The interventions carried out by the government of Sabang have dramatically reduced the burden of malaria over the past seven years. The first phase, carried out between 2005 and 2007, included improved

  1. RNA extraction from ten year old formalin-fixed paraffin-embedded breast cancer samples: a comparison of column purification and magnetic bead-based technologies

    Directory of Open Access Journals (Sweden)

    Zhang Haiyu

    2007-12-01

    Full Text Available Abstract Background The development of protocols for RNA extraction from paraffin-embedded samples facilitates gene expression studies on archival samples with known clinical outcome. Older samples are particularly valuable because they are associated with longer clinical follow up. RNA extracted from formalin-fixed paraffin-embedded (FFPE tissue is problematic due to chemical modifications and continued degradation over time. We compared quantity and quality of RNA extracted by four different protocols from 14 ten year old and 14 recently archived (three to ten months old FFPE breast cancer tissues. Using three spin column purification-based protocols and one magnetic bead-based protocol, total RNA was extracted in triplicate, generating 336 RNA extraction experiments. RNA fragment size was assayed by reverse transcription-polymerase chain reaction (RT-PCR for the housekeeping gene glucose-6-phosphate dehydrogenase (G6PD, testing primer sets designed to target RNA fragment sizes of 67 bp, 151 bp, and 242 bp. Results Biologically useful RNA (minimum RNA integrity number, RIN, 1.4 was extracted in at least one of three attempts of each protocol in 86–100% of older and 100% of recently archived ("months old" samples. Short RNA fragments up to 151 bp were assayable by RT-PCR for G6PD in all ten year old and months old tissues tested, but none of the ten year old and only 43% of months old samples showed amplification if the targeted fragment was 242 bp. Conclusion All protocols extracted RNA from ten year old FFPE samples with a minimum RIN of 1.4. Gene expression of G6PD could be measured in all samples, old and recent, using RT-PCR primers designed for RNA fragments up to 151 bp. RNA quality from ten year old FFPE samples was similar to that extracted from months old samples, but quantity and success rate were generally higher for the months old group. We preferred the magnetic bead-based protocol because of its speed and higher quantity of

  2. Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants

    Directory of Open Access Journals (Sweden)

    Anchang Judith

    2008-01-01

    Full Text Available Abstract Background Individuals living in malaria endemic areas generally harbour multiple parasite strains. Multiplicity of infection (MOI can be an indicator of immune status. However, whether this is good or bad for the development of immunity to malaria, is still a matter of debate. This study aimed to examine the MOI in asymptomatic children between two and ten years of age and to relate it to erythrocyte variants, clinical attacks, transmission levels and other parasitological indexes. Methods Study took place in Niakhar area in Senegal, where malaria is mesoendemic and seasonal. Three hundred and seventy two asymptomatic children were included. Sickle-cell trait, G6PD deficiency (A- and Santamaria and α+-thalassaemia (-α3.7 type were determined using PCR. Multiplicity of Plasmodium falciparum infection, i.e. number of concurrent clones, was defined by PCR-based genotyping of the merozoite surface protein-2 (msp2, before and at the end of the malaria transmission season. The χ2-test, ANOVA, multivariate linear regression and logistic regression statistical tests were used for data analysis. Results MOI was significantly higher at the end of transmission season. The majority of PCR positive subjects had multiple infections at both time points (64% before and 87% after the transmission season. MOI did not increase in α-thalassaemic and G6PD mutated children. The ABO system and HbAS did not affect MOI at any time points. No association between MOI and clinical attack was observed. MOI did not vary over age at any time points. There was a significant correlation between MOI and parasite density, as the higher parasite counts increases the probability of having multiple infections. Conclusion Taken together our data revealed that α-thalassaemia may have a role in protection against certain parasite strains. The protection against the increase in MOI after the transmission season conferred by G6PD deficiency is probably due to clearance of

  3. Phenylpropanoid ester from Zingiber officinale and their inhibitory effects on the production of nitric oxide.

    Science.gov (United States)

    Hong, Seong Su; Oh, Joa Sub

    2012-02-01

    A new phenylpropanoid ester mixture, (E)-geranylferulic acid (1a) and (Z)-geranylferulic acid (1b), along with 13 known compounds, [6]-gingerol (2), [8]-gingerol (3), [10]-gingerdione (4), 1-dehydro-[6]-gingerdione (5), 1-dehydro-[8]-gingerdione (6), [6]-paradol (7), [8]-paradol (8), [6]-gingeroldiacetate (9), 6-hydroxy-[6]-shogaol (10), galanolactone (11), trans-®-sesquiphellandrol (12), trans-sesquipiperitol (13), and 4α,5β-dihydroxybisabola-2,10-diene (14) were isolated from ethanol extract of Zingiber officinale. Their structures were determined based on the spectroscopic (1D, 2D-NMR and MS) and chemical evidence. All of the isolates were evaluated for their potential to inhibit LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells. Compounds 1-12 were found to inhibit nitric oxide production with IC(50) values ranging from 5.5 to 28.5 μM.

  4. Alkaloids of Vinca rosea L. (Catharanthus roseus G. Don). 38. 4'-Dehydrated derivatives.

    Science.gov (United States)

    Miller, J C; Gutowski, G E; Poore, G A; Boder, G B

    1977-03-01

    A series of 4'-dehydrated derivatives of various dimeric Vinca alkaloids has been synthesized to further define the structure-activity relationships of Vinca alkaloids with onolytic potency. The concentrated sulfuric acid dehydration in most cases gave mixtures of the 3',4'-and two isomeric 4',20'-alkenes, which were isolated and characterized primarily by proton and 13C NMR. Compound tested for antitumor activity include the three dehydro isomers of 4'-deacetylvinblastine, 4-deacetylvincristine, and 4-deacetylvinblastine-23-amide and some4'-dehydrated derivatives epimeric at C-18'. Generally, the decrease in toxicity imparted by the new double bond was accompained by a decrease in potency. An exception was 3',4'-dehydro-4-deacetylvincristine, which showed a decrease in toxicity and increase in potency against at least one tumor in which vincristine itself has little effect.

  5. Two new triterpenoids from the resin of Boswellia carterii.

    Science.gov (United States)

    Wang, Feng; Li, Zhan-Lin; Cui, Hong-Hua; Hua, Hui-Ming; Jing, Yong-Kui; Liang, Sheng-Wang

    2011-03-01

    Two new triterpenoids, 3-oxotirucalla-7,9(11),24-trien-21-oic acid (1) and 18Hα,3β,20β-ursanediol (2), along with 15 known triterpenes, α-amyrin, α-boswellic acid, β-boswellic acid, acetyl α-boswellic acid, acetyl β-boswellic acid, 9,11-dehydro-β-boswellic acid, 9,11-dehydro-α-boswellic acid, acetyl 11α-methoxy-β-boswellic acid, 11-keto-β-boswellic acid, acetyl 11-keto-β-boswellic acid, acetyl α-elemolic acid, 3β-hydroxytirucalla-8,24-dien-21-oic acid, elemonic acid, 3α-hydroxytirucalla-7,24-dien-21-oic acid, and 3α-hydroxytirucall-24-en-21-oic acid, were isolated from the resin of Boswellia carterii Birdw.

  6. Role of 11β-OH-C(19) and C(21) steroids in the coupling of 11β-HSD1 and 17β-HSD3 in regulation of testosterone biosynthesis in rat Leydig cells.

    Science.gov (United States)

    Latif, Syed A; Shen, Mae; Ge, Ren-Shan; Sottas, Chantal M; Hardy, Matthew P; Morris, David J

    2011-06-01

    Here we describe further experiments to support our hypothesis that bidirectional 11β-HSD1-dehydrogenase in Leydig cells is a NADP(H) regenerating system. In the absence of androstenedione (AD), substrate for 17β-HSD3, incubation of Leydig cells with corticosterone (B) or several C(19)- and C(21)-11β-OH-steroids, in the presence of [(3)H]-11-dehydro-corticosterone (A), stimulated 11β-HSD1-reductase activity. However, in presence of 30 μM AD, testosterone (Teso) synthesis is stimulated from 4 to 197 picomole/25,000 cells/30 min and concomitantly inhibited 11β-HSD1-reductase activity, due to competition for the common cofactor NADPH needed for both reactions. Testo production was further significantly increased (psteroids (in addition to 30 μM AD) were also included. Similar results were obtained in experiments conducted with lower concentrations of AD (5 μM), and B or A (500 nM). Incubations of 0.3-6.0 μM of corticosterone (plus or minus 30 μM AD) were then performed to test the effectiveness of 17β-HSD3 as a possible NADP(+) regenerating system. In the absence of AD, increasing amounts (3-44 pmol/25,000 cells/30 min) of 11-dehydro-corticosterone were produced with increasing concentrations of corticosterone in the medium. When 30 μM AD was included, the rate of 11-dehydro-corticosterone formation dramatically increased 1.3-5-fold producing 4-210 pmol/25,000 cells/30 min of 11-dehydro-corticosterone. We conclude that 11β-HSD1 is enzymatically coupled to 17β-HSD3, utilizing NADPH and NADP in intermeshed regeneration systems.

  7. Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate

    OpenAIRE

    Celia Bustos-Brito; Valeria J. Vázquez-Heredia; Fernando Calzada; Lilian Yépez-Mulia; José S. Calderón; Simón Hernández-Ortega; Baldomero Esquivel; Normand García-Hernández; Leovigildo Quijano

    2016-01-01

    Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2) and 10-be...

  8. The concentration of ammonia regulates nitrogen metabolism in Saccharomyces cerevisiae.

    OpenAIRE

    ter Schure, E G; Silljé, H H; Verkleij, A J; Boonstra, J; Verrips, C T

    1995-01-01

    Saccharomyces cerevisiae was grown in a continuous culture at a single dilution rate with input ammonia concentrations whose effects ranged from nitrogen limitation to nitrogen excess and glucose limitation. The rate of ammonia assimilation (in millimoles per gram of cells per hour) was approximately constant. Increased extracellular ammonia concentrations are correlated with increased intracellular glutamate and glutamine concentrations, increases in levels of NAD-dependent glutamate dehydro...

  9. Urease inhibitory activities of beta-boswellic acid derivatives

    OpenAIRE

    Reza Hajiaghaee; Behnam Yousefi; Zinat Bahrampour Omrany; Farzaneh Nabati; Sahand Golestanian; Roya Bazl; Sanaz Golbabaei; "Shamsali Rezazadeh; Massoud Amanlou

    2013-01-01

    Background and the purpose of the study: Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative.Methods 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-beta-boswellic acid; 2, 3-O-acetyl-11-hydrox...

  10. Urease inhibitory activities of β-boswellic acid derivatives

    OpenAIRE

    Amanlou Massoud; Rezazadeh Shamsali; Hajiaghaee Reza; Nabati Farzaneh; Yousefi Behnam; Omrany Zinat Bahrampour; Golestanian Sahand; Bazl Roya; Golbabaei Sanaz

    2013-01-01

    Abstract Background and the purpose of the study Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. Methods 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-...

  11. CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein.

    Science.gov (United States)

    Tang, Lichun; Zeng, Yanting; Du, Hongzi; Gong, Mengmeng; Peng, Jin; Zhang, Buxi; Lei, Ming; Zhao, Fang; Wang, Weihua; Li, Xiaowei; Liu, Jianqiao

    2017-03-01

    Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.

  12. Indigenous populations in Mexico: medical anthropology in the work of Ruben Lisker in the 1960s.

    Science.gov (United States)

    Suárez-Díaz, Edna

    2014-09-01

    Ruben Lisker's research on the genetic hematological traits of Mexican indigenous populations illustrates the intersection of international health policies and the local modernizing nationalism of the Mexican post-revolution period. Lisker's surveys of blood group types, and of G6PD (glucose-6-phosphodehydrogenase) and hemoglobin variants in indigenous populations, incorporated linguistic criteria in the sampling methods, and historical and cultural anthropological accounts in the interpretation of results. In doing so, Lisker heavily relied on the discourse and the infrastructure created by the indigenista program and its institutions. Simultaneously, Lisker's research was thoroughly supported by international and bilateral agencies and programs, including the malaria eradication campaign of the 1950s and 1960s. As a member of the scientific elite he was able to make original contributions to the postwar field of human population genetics. His systematic research illustrates the complex entanglement of local and international contexts that explains the co-construction of global knowledge on human variation after WWII.(1.)

  13. Modes of risk explanation in telephone consultations between nurses and parents for a genetic condition

    DEFF Research Database (Denmark)

    Zayts, Olga; Sarangi, Srikant

    2013-01-01

    consultations in Hong Kong between genetic nurses and parents whose infants have been diagnosed with a mild hereditary disorder, G6PD deficiency, commonly known as favism. Using discourse analytic methods, we focus on 50 audio-recorded telephone consultations. First, we show the distribution of different types...... of risk explanation in terms of their volume and sequential positioning in the study corpus. The two predominant explanation types – physiological explanations and hereditary explanations – are then discussed in relation to their respective functions in these telephone consultations, namely serving...... or absence of prior knowledge of the condition on the part of the parents; and these differences are displayed at the interactional rather than at the substantive level, that is parents with prior knowledge of the condition occupy a different participant status in eliciting and responding to the risk...

  14. Diabetic Wound Healing and Activation of Nrf2 by Herbal Medicine

    Science.gov (United States)

    Senger, Donald R.; Cao, Shugeng

    2016-01-01

    Nrf2 defense is a very important cellular mechanism to control oxidative stress, which is implicated in wound healing. Nrf2 can induce many cytoprotective genes, including HO-1, NQO1 and G6PD. Among many natural products that have been reported as Nrf2 activators, sulforaphane and curcumin have been studied more widely than any others, and both are in clinical trials for non-cancerous disorders. Recently, we reported 4-ethyl catechol and 4-vinyl catechol as Nrf2 co-factors that can induce Nrf2 as potently as sulforaphane and curcumin. These new Nrf2 co-factors were identified in hot aqueous extract of an herbal medicine Barleria lupulina, and fermented Noni (Morinda citrifolia) juice, which are used traditionally for diabetic wound healing. PMID:27868087

  15. Protective Effect of Troxerutin on Nickel-Induced Testicular Toxicity in Wistar Rats.

    Science.gov (United States)

    Elangovan, Perumal; Jalaludeen, Abdulkadhar Mohamed; Ramakrishnan, Ramalingam; Pari, Leelavinothan

    2016-01-01

    Nickel (Ni)-induced oxidative damage is a serious problem that leads to reproductive system failure through testicular damage. The present investigation was carried out to determine the effect of troxerutin (Txn) on testicular toxicity induced by Ni in experimental rat testes. The oral administration of Txn (100 mg/kg body weight [bw]) showed a significant (p glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), reduced glutathione, ascorbate, total sulphydryl groups, and testis-organ weight. Subsequently, the administration of Txn also significantly reduced the accumulation of Ni, lipid peroxidation products, and protein carbonyl levels in Txn-treated animals. Testicular protection in the experimental animals by Txn is further substantiated by a remarkable reduction of Ni, which was revealed through testicular tissue histopathology. These studies suggest that Txn could prevent oxidative damage and testicular toxicity induced by Ni in experimental animals.

  16. Review: Malaria chemoprophylaxis for travelers to Latin America.

    Science.gov (United States)

    Steinhardt, Laura C; Magill, Alan J; Arguin, Paul M

    2011-12-01

    Because of recent declining malaria transmission in Latin America, some authorities have recommended against chemoprophylaxis for most travelers to this region. However, the predominant parasite species in Latin America, Plasmodium vivax, can form hypnozoites sequestered in the liver, causing malaria relapses. Additionally, new evidence shows the potential severity of vivax infections, warranting continued consideration of prophylaxis for travel to Latin America. Individualized travel risk assessments are recommended and should consider travel locations, type, length, and season, as well as probability of itinerary changes. Travel recommendations might include no precautions, mosquito avoidance only, or mosquito avoidance and chemoprophylaxis. There are a range of good options for chemoprophylaxis in Latin America, including atovaquone-proguanil, doxycycline, mefloquine, and--in selected areas--chloroquine. Primaquine should be strongly considered for nonpregnant, G6PD-nondeficient patients traveling to vivax-endemic areas of Latin America, and it has the added benefit of being the only drug to protect against malaria relapses.

  17. Pycnogenol防缺乏G6PD的红细胞受到溶血损害

    Institute of Scientific and Technical Information of China (English)

    靳淑敏; 刘会臣

    2004-01-01

    葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症是人类最常见的酶病。缺乏G6PD的红细胞无足够的能力破坏过氧化物,并对溶血有较高的易感性。Pycnogenol是用法国海岸松树皮制得的含原花青素和双黄酮类成分的干浸膏,作者研究了该制剂是否能预防缺乏G6PD的红细胞免受溶血损害。

  18. 324Pycnogenol(R)预防缺乏G6PD的红细胞受到溶血损害

    Institute of Scientific and Technical Information of China (English)

    靳淑敏; 刘会臣

    2004-01-01

    @@ 葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症是人类最常见的酶病.缺乏G6PD的红细胞无足够的能力破坏过氧化物,并对溶血有较高的易感性.Pycnogenol是用法国海岸松树皮制得的含原花青素和双黄酮类成分的干浸膏,作者研究了该制剂是否能预防缺乏G6PD的红细胞免受溶血损害.

  19. Anaemia, a common but often unrecognized risk in diabetic patients: a review.

    Science.gov (United States)

    Angelousi, A; Larger, E

    2015-02-01

    Anaemia in patients with diabetes, both type 1 and type 2, is a frequent clinical finding. The mechanisms of anaemia are multifactorial and often not very well understood. Iatrogenic causes, including oral antidiabetic drugs, ACE inhibitors and ARBs, and renal insufficiency are the major causes of anaemia in patients with type 2 diabetes. In patients with type 1, the cause is often an associated autoimmune disease, and screening for autoimmune gastritis, pernicious anaemia, Hashimoto's thyroiditis, coeliac disease and Addison's disease is recommended. Other rare causes - including G6PD deficiency, microangiopathic haemolytic anaemia and thiamine-responsive megaloblastic anaemia - should be suspected in young patients or when the classical causes are excluded. Early detection and recognition of the cause(s) of anaemia in patients with diabetes could help to prevent other clinical manifestations as well as the complications of diabetes.

  20. 巨型艾美耳球虫(Eimeria maxima)地理株研究Ⅲ.11株巨型艾美耳球虫的同工酶分析%Geographical strains of Eimeria maxima Ⅲ. Analysis on isozymes of eleven geographical strains of E. maxima

    Institute of Scientific and Technical Information of China (English)

    李文超; 陶建平; 顾有方; 沈永林

    2008-01-01

    采用聚丙烯酰胺凝胶垂直板电泳(PAGE)技术.对11株Eimeria maxima和1株E.tenella的孢子化卵囊,进行了乳酸脱氢酶(LDH)、葡萄糖磷酸异构酶(GPI)、葡萄糖-6-磷酸脱氢酶(G6PD)、葡萄糖磷酸变位酶(PGM)和苹果酸脱氢酶(MDH)的同工酶分析.试验结果显示,E.maxima和E.tenella在LDH、GPI、G6PD、PGM和MDH的酶谱上有明显差异,而在11株E.maxima之间无差异,表明E.maxima的酶变异相当保守.

  1. Deficiencia de glucosa-6-fosfato deshidrogenasa en un paciente con síndrome de Down

    OpenAIRE

    Francisco R. Cammarata Scalisi; Harry Sánchez; Graciela Cammarata Scalisi; Nayra Cabral Alfonso; Osmoire Moreno; Miguel Alonzo Bastardo Ramos; Gustavo Gil

    2012-01-01

    El síndrome de Down, es una alteración genética que ocurre cuando un individuo exhibe todo o una parte específica adicional del cromosoma 21 y es la entidad más frecuentemente asociada a retardo mental. La deficiencia de glucosa-6-fosfato deshidrogenasa, es el defecto enzimático más común en humanos y presenta patrón de herencia ligado al cromosoma X recesivo. Se debe a la mutación del gen G6PD, el cual causa diversos fenotipos bioquímicos y clínicos. Reportamos un caso de lactante menor masc...

  2. [Common anemias in neonatology].

    Science.gov (United States)

    Humbert, J; Wacker, P

    1999-01-28

    We describe the four most common groups of neonatal anemia and their treatments, with particular emphasis on erythropoietin therapy. The hemolytic anemias include the ABO incompatibility (much more frequent, nowadays, than the Rh incompatibility, which has nearly disappeared following the use of anti-D immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G-6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19 predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin transfusions, or during feto-maternal transfusions. Finally, the multifactorial anemia of prematurity develops principally as a result of the rapid expansion of the blood volume in this group of patients. Erythropoietin therapy, often at doses much higher than those used in the adult, should be seriously considered in most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of transfusions.

  3. Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer.

    Science.gov (United States)

    Monsó, Eduard; Montuenga, Luis M; Sánchez de Cos, Julio; Villena, Cristina

    2015-09-01

    The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel.

  4. Convergent evolution to an aptamer observed in small populations on DNA microarrays

    Science.gov (United States)

    Rowe, W.; Platt, M.; Wedge, D. C.; Day, P. J. R.; Kell, D. B.; Knowles, J. D.

    2010-09-01

    The development of aptamers on custom synthesized DNA microarrays, which has been demonstrated in recent publications, can facilitate detailed analyses of sequence and fitness relationships. Here we use the technique to observe the paths taken through sequence-fitness space by three different evolutionary regimes: asexual reproduction, recombination and model-based evolution. The different evolutionary runs are made on the same array chip in triplicate, each one starting from a small population initialized independently at random. When evolving to a common target protein, glucose-6-phosphate dehydrogenase (G6PD), these nine distinct evolutionary runs are observed to develop aptamers with high affinity and to converge on the same motif not present in any of the starting populations. Regime specific differences in the evolutions, such as speed of convergence, could also be observed.

  5. Efeito do uso de óleo na dieta sobre a lipogênese e o perfil lipídico de tilápias-do-nilo Effect of different oils in the diet on lipogenesis and the lipid profile of nile tilapias

    Directory of Open Access Journals (Sweden)

    Paula Adriane Perez Ribeiro

    2008-08-01

    Full Text Available Trinta e cinco machos de tilápia com peso médio de 205 g foram mantidos em caixas de 250 litros para avaliar o metabolismo lipídico de tilápias-do-nilo (Oreochromis niloticus. O experimento foi conduzido durante 30 dias, entre os meses de outubro e novembro de 2006. Foram avaliadas cinco dietas, cada uma contendo óleo de oliva, óleo de milho, óleo de soja, óleo de linhaça ou óleo de peixe. Utilizou-se delineamento inteiramente casualizado, com cinco tratamentos e sete repetições. Avaliaram-se a composição química, o perfil lipídico muscular e a atividade hepática de glicose-6-P desidrogenase (G6PD e enzima málica. Os dados foram submetidos à análise de variância com médias comparadas pelo teste de Scott-Knott (5%. Não houve diferenças significativas para os teores de umidade e cinzas, porém, foram observadas alterações nos teores de lipídios e proteína nos peixes alimentados com as rações contendo óleo de oliva, milho ou soja. O fornecimento de dietas ricas em ácidos graxos poliinsaturados aumentou a composição desses ácidos graxos nos peixes. A atividade da G6PD foi superior à da enzima málica e foi mais alta nos animais alimentados com rações contendo óleos de oliva, milho ou soja, o que evidencia maior deposição lipídica muscular nesses peixes.A total of 35 males of Nile tilapia, averaging initial weight of 205 g, were maintained in five 250 L metabolism boxes to evaluate the lipid metabolism of Nile tilapias (Oreochromis niloticus. The experiment lasted 30 days, from October to November 2006. The treatments were: control diet plus olive oil; control diet plus corn oil; control diet plus soybean oil; control diet plus linseed oil; control diet plus fish oil. The experiment was in a completely randomized design with five treatments and seven replicates. The evaluated parameters were: fatty acid profile of the muscle tissue and hepatic activity of glucose-6-phosphate dehydrogenase (G6PD and malic

  6. The association between malaria parasitaemia, erythrocyte polymorphisms, malnutrition and anaemia in children less than 10 years in Senegal

    DEFF Research Database (Denmark)

    Tine, Roger C K; Ndiaye, Magatte; Hansson, Helle Holm

    2012-01-01

    BACKGROUND:Malaria and anaemia (Haemoglobin= 11 g/dl. For each participant, a physical examination was done and anthropometric data collected prior to a biological assessment which included: malaria parasitaemia infection, intestinal worm carriage, G6PD deficiency, sickle cell disorders, and alpha......-talassaemia.RESULTS:Three hundred and fifty two children 5 years (aOR=0.03, 95%CI0.01-0.08]). Stratified by age group, anaemia was significantly associated with stunting in children less than 5 years (aOR=3.1 95%CI1.4 -- 6.8]), with, sickle cell disorders (aOR=3.5 95%CI 1.4 -- 9.0]), alpha-thalassemia (or=2.4 95%CI1...

  7. Purification of glucose-6-phosphate dehydrogenase and glutathione reductase enzymes from the gill tissue of Lake Van fish and analyzing the effects of some chalcone derivatives on enzyme activities.

    Science.gov (United States)

    Kuzu, Muslum; Aslan, Abdulselam; Ahmed, Ishtiaq; Comakli, Veysel; Demirdag, Ramazan; Uzun, Naim

    2016-04-01

    Glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR) are metabolically quite important enzymes. Within this study, these two enzymes were purified for the first time from the gills of Lake Van fish. In the purifying process, ammonium sulfate precipitation and 2',5'-ADP Sepharose 4B affinity column chromatography techniques for glucose-6-phosphate dehydrogenase, temperature degradation and 2',5'-ADP Sepharose 4B affinity column chromatography for glutathione reductase enzyme were used. The control of the enzyme purity and determination of molecular weight were done with sodium dodecyl sulfate polyacrylamide gel electrophoresis. K(M) and V(max) values were determined with Lineweaver-Burk plot. Besides, the effects of some chalcone derivatives on the purified enzymes were analyzed. For the ones showing inhibition effect, % activity-[I] figures were drawn and IC50 values were determined. K(i) value was calculated by using Cheng-Prusoff equation.

  8. Rh-catalyzed asymmetric hydrogenation of prochiral olefins with a dynamic library of chiral TROPOS phosphorus ligands.

    Science.gov (United States)

    Monti, Chiara; Gennari, Cesare; Piarulli, Umberto; de Vries, Johannes G; de Vries, André H M; Lefort, Laurent

    2005-11-04

    A library of 19 chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P-bound alcohol (11 phosphites) or secondary amine (8 phosphoramidites), was synthesized. These ligands were screened, individually and as a combination of two, in the rhodium-catalyzed asymmetric hydrogenation of dehydro-alpha-amino acids, dehydro-beta-amino acids, enamides and dimethyl itaconate. ee values up to 98% were obtained for the dehydro-alpha-amino acids, by using the best combination of ligands, a phosphite [4-P(O)2O] and a phosphoramidite [13-P(O)2N]. Kinetic studies of the reactions with the single ligands and with the combination of phosphite [4-P(O)2O] and phosphoramidite [13-P(O)2N] have shown that the phosphite, despite being less enantioselective, promotes the hydrogenation of methyl 2-acetamidoacrylate and methyl 2-acetamidocinnamate faster than the mixture of the same phosphite with the phosphoramidite, while the phosphoramidite alone is much less active. In this way, the reaction was optimized by lowering the phosphite/phosphoramidite ratio (the best ratio is 0.25 equiv phosphite/1.75 equiv phosphoramidite) with a resulting improvement of the product enantiomeric excess. A simple mathematical model for a better understanding of the variation of the enantiomeric excess with the phosphite/phosphoramidite ratio is also presented.

  9. 9-Glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine Is the Major Pyrrolic Glutathione Conjugate of Retronecine-Type Pyrrolizidine Alkaloids in Liver Microsomes and in Rats.

    Science.gov (United States)

    Chen, Meixia; Li, Liang; Zhong, Dafang; Shen, Shuijie; Zheng, Jiang; Chen, Xiaoyan

    2016-02-15

    Retronecine-, otonecine-, and heliotridine-type pyrrolizidine alkaloids (PAs) are all reported to be hepatotoxic. These PAs are suggested to be metabolized to the corresponding electrophilic dehydropyrrolizidine alkaloids (dehydro-PAs) and subsequently conjugated with macromolecules, such as glutathione (GSH). In the present study, a total of five glutathione conjugates, named M1-M5, were detected in rat and human liver microsomal incubations with three retrornecine-type PAs (isoline, retrorsine, or monocrotaline) in the presence of glutathione, and were chemically synthesized. M1 and M3 were unambiguously identified as a pair of epimers of 7-glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7-GSH-DHP), and M4 and M5 were epimers of 7,9-diglutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7,9-diGSH-DHP). M2, an extremely unstable conjugate, was proposed to be 9-glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (9-GSH-DHP). It was the most abundant among the five GSH conjugates, and the finding corrects the mistake that 7-GSH-DHP is the predominant GSH conjugate derived from dehydro-PAs. Similar patterns in glutathione conjugate profile were observed in the bile of rats treated with the PAs. This is the first study to describe 9-GSH-DHP as a major pyrrolic GSH conjugate of retronecine-type PAs, providing insight into the interactions of dehydro-PAs with biomolecules.

  10. Diet Rich in Saturated Fat Decreases the Ratio of Thromboxane/prostacyclin in Healthy Men

    Institute of Scientific and Technical Information of China (English)

    DUO LI; RAYMUNDO HABITO; GEORGE ANGELOS; ANDREW J. SINCLAIR; MADELEINE J. BALL

    2003-01-01

    Objective To investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane B2 (TXB2) and 6-keto prostaglandin F 1α (PGF 1α) in 27 healthy free-living male subjects aged 30 to 55 years. Methods It was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a ‘wash-out period',before being assigned to the other diet for an additional 4 weeks. Results Serum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF 1α (P<0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2. Conclusions Diet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

  11. Evaluation of Potential Pharmacokinetic Drug-Drug Interaction between Armodafinil and Aripiprazole in Healthy Adults.

    Science.gov (United States)

    Darwish, M; Bond, M; Yang, R; Hellriegel, E T; Robertson, P

    2015-07-01

    Armodafinil, a moderate inducer of cytochrome P450 (CYP) 3A4, has been studied as adjunctive therapy to maintenance medications for major depressive episodes associated with bipolar I disorder. We evaluated the effect of daily dosing with armodafinil on the pharmacokinetics and safety of the CYP3A4 substrate aripiprazole, an atypical antipsychotic used to treat bipolar I disorder. Healthy adults received 15 mg aripiprazole alone and after armodafinil (250 mg/day) pretreatment. Pharmacokinetic parameters were derived from plasma concentrations of aripiprazole and its active metabolite, dehydro-aripiprazole, obtained over 16 days after each aripiprazole administration. Steady-state pharmacokinetics of armodafinil and its 2 circulating metabolites was assessed. Of 36 subjects enrolled, 24 were evaluable for pharmacokinetic analysis. Armodafinil reduced systemic exposure to aripiprazole (Cmax, - 8%; AUC0-∞, -34%) and dehydro-aripiprazole, which is both formed and eliminated in part via CYP3A4 (Cmax, - 10%; AUC0-∞, - 32%). Adverse events were generally consistent with known safety profiles of each agent. Systemic exposure to aripiprazole and dehydro-aripiprazole was moderately reduced following armodafinil pretreatment. The combination was generally well tolerated under the conditions studied. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T/sub 3/ generation

    Energy Technology Data Exchange (ETDEWEB)

    Bianco, A.C.; Silva, J.E.

    1987-09-01

    The authors have examined the activity of three lipogenic enzymes (malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), and acetyl coenzyme A (CoA) carboxylase), the activity of the mitochondrial FAD-dependent ..cap alpha..-glycerolphosphate dehydrogenase (..cap alpha..-GPD), and the mitochondrial concentration of uncoupling protein (UCP) in brown adipose tissue (BAT) of euthyroid and hypothyroid rats, both at room temperature and in response to acute cold stress. These enzymes and UCP are important for the thermogenic response of BAT in adaptation to cold. The basal level of the lipogenic enzymes was normal or slightly elevated in hypothyroid rats maintained at 23/sup 0/C, but the levels of ..cap alpha..-GPD and UCP were markedly reduced. Forty-eight hours at 4/sup 0/C resulted in an increase in the activity of G-6-PD, acetyl-CoA carboxylase, and ..cap alpha..-GPD and in the concentration of UCP both in euthyroid and hypothyroid animals, but the levels reached were invariably less in hypothyroid animals, indicating that thyroid hormone is necessary for a full metabolic response of BAT under maximal demands. Of all variables measured, the most affected was UCP followed by ..cap alpha..-GDP. Dose-response relationship analysis of the UCP response to T/sub 3/ indicated that the normalization of the response to cold requires saturation of the nuclear T/sub 3/ receptors. They concluded, therefore, that the activation of the BAT 5'-deiodinase induced by cold exposure is essential to provide the high levels of nuclear T/sub 3/ required for the full expression of BAT thermogenic potential.

  13. Growth performance and antioxidant enzyme activities in rainbow trout (Oncorhynchus mykiss) juveniles fed diets supplemented with sage, mint and thyme oils.

    Science.gov (United States)

    Sönmez, Adem Yavuz; Bilen, Soner; Alak, Gonca; Hisar, Olcay; Yanık, Talat; Biswas, Gouranga

    2015-02-01

    This study evaluated effects of dietary supplementation of sage (Salvia officinalis), mint (Mentha spicata) and thyme (Thymus vulgaris) oils on growth performance, lipid peroxidation level (melondialdehyde, MDA) and liver antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; glucose-6-phosphate dehydrogenase, G6PD; glutathione reductase, GR; glutathione-S-transferase, GST and glutathione peroxidase, GPx) in rainbow trout (Oncorhynchus mykiss) juveniles. For this purpose, triplicate groups of rainbow trout were fed daily ad libitum with diets containing sage, mint and thyme oils at 500, 1,000 and 1,500 mg kg(-1) for 60 days. While weight gain percentage of fish fed the diets containing sage and thyme oils was significantly higher than the control group, that of fish fed mint oil was the lowest. Similarly, specific growth rate was found to be the highest in all groups of the sage and thyme oil feeding and the lowest in the mint groups. Moreover, feed conversion ratio was significantly higher in the mint oil administered groups. Survival rate was also significantly reduced in the fish fed the diet containing mint oil. It was observed that SOD, G6PD and GPx activities were significantly increased in liver tissues of all the treated fish groups compared to that of control diet-fed group. However, CAT, GST and GR activities were significantly decreased in experimental diet-fed fish groups at the end of the experiment. On the other hand, a significant reduction was found in MDA levels in the fish fed the diets with sage and thyme oils compared to control and mint diets on the 30th and 60th days of experiment. Overall, dietary inclusion of sage and thyme oils is effective in enhancing rainbow trout growth, reduction in MDA and least changing antioxidant enzyme activities at a low level of 500 mg kg(-1) diet, and they can be used as important feed supplements for rainbow trout production.

  14. Evaluation of antimalarial activity and toxicity of a new primaquine prodrug.

    Directory of Open Access Journals (Sweden)

    Marcelo Gomes Davanço

    Full Text Available Plasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of primaquine (PQ and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe-Ala-PQ is a PQ prodrug with a more favorable pharmacokinetic profile compared to PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human hepatoma cell line (HepG2, a monkey kidney cell line (BGM, and human red blood cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD. In addition, in vivo toxicity assays were performed with rats that received multiple doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological parameters. The activity was assessed by the inhibition of the sporogonic cycle using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2 cells and caused less hemolysis of G6PD-deficient red blood cells at similar concentrations. The prodrug caused less alteration in the biochemical parameters than did PQ. Histopathological analysis of the liver and kidney did show differences between the control and Phe-Ala-PQ-treated groups, but they were not statistically significant. Taken together, the results highlight the prodrug as a novel lead compound candidate for the treatment of P. vivax malaria and as a blocker of malaria transmission.

  15. Alterations in energy/redox metabolism induced by mitochondrial and environmental toxins: a specific role for glucose-6-phosphate-dehydrogenase and the pentose phosphate pathway in paraquat toxicity.

    Science.gov (United States)

    Lei, Shulei; Zavala-Flores, Laura; Garcia-Garcia, Aracely; Nandakumar, Renu; Huang, Yuting; Madayiputhiya, Nandakumar; Stanton, Robert C; Dodds, Eric D; Powers, Robert; Franco, Rodrigo

    2014-09-19

    Parkinson's disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat "hijacks" the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations in

  16. 不同麻醉方法对老年结直肠癌手术患者白细胞糖代谢的影响%EffectsofDifferentMethodsofAnesthesiaMetabolism inPatientswithRectalCancerOperationWhiteBlood CellsofElderlyPatientswithSugar

    Institute of Scientific and Technical Information of China (English)

    卢先卿

    2013-01-01

      目的探讨不同麻醉方法对老年结直肠癌手术患者白细胞糖代谢的影响。方法抽取我院68例老年结直肠癌患者,随机均分对照组和观察组,分别在手术时采取七氟醚吸入麻醉和七氟醚吸入联合硬膜外阻滞麻醉。结果麻醉后两组患者白细胞计数、白细胞内PK以及G6PD活性均明显升高(P<0.05),且观察组较对照组高(P<0.05)。结论以上两种麻醉方式对白细胞内PK、G6PD活性的影响有明显差别,联合麻醉法影响最大。%Objective The effect of different methods of anesthesia metabolism in patients with rectal cancer operation white blood cells of elderly patients with sugar. Method Selected in our hospital 68 cases of elderly patients with colorectal cancer, were randomly and equally divided into control group and observation group, take the sevolfurane inhaled anesthesia and sevolfurane inhalation combined with epidural anesthesia in the operation. Result After anesthesia, white blood cell count, two groups of patients in white blood cells of PK and G6PD activity were signiifcantly increased (P<0.05), and the observation group than in the control group (P<0.05). Conclusion There are obvious differences between the above two kinds of anesthesia methods on intracellular PK, G6PD activity, combined anesthesia effect.

  17. Involvement of glutathione transferases, Gtt1and Gtt2, with oxidative stress response generated by H2O2 during growth of Saccharomyces cerevisiae.

    Science.gov (United States)

    Mariani, Diana; Mathias, Cristiane J; da Silva, Carmelita G; Herdeiro, Ricardo da Silva; Pereira, Ricardo; Panek, Anita D; Eleutherio, Elis C A; Pereira, Marcos Dias

    2008-01-01

    Glutathione transferases are detoxifying enzymes responsible for eliminating toxic compounds generated under a variety of stress conditions. Saccharomyces cerevisiae control cells and glutathione transferase mutant strains (gtt1 and gtt2) were used to analyze tolerance, lipid and protein oxidation as oxidative stress markers during growth in the presence of H2O2. Glucose 6-phosphate dehydrogenase (G6PD) and glutathione reductase were assayed to monitor the capacity of cells to recycle glutathione. Although a reduction in growth was observed, deletion of GTT1 showed less inhibition by H2O2 than the control strain. Cells showed a significant reduction in cellular viability during the first hours of growth, the gtt1 mutant being hypersensitive even after 24 h of H2O2 exposure. As a consequence of oxidative stress caused by exposure to H2O2, an increase in lipid peroxidation was observed, mainly in the glutathione transferase mutant strains. While protein carbonylation increased by 17% and 23%, respectively, after 2 h in the presence of H2O2 in the control and gtt2 mutant, a 40% increase was observed in the gtt1 strain after 24-h exposure. The antioxidant G6PD and glutathione reductase activities were affected in the gtt1 mutant during H2O2 exposure, which could be critical for recycling glutathione. The same was observed for the gtt2 mutant after 2-h treatment, indicating that glutathione recycling might be associated with the detoxification process. Thus, glutathione transferases, Gtt1 and Gtt2, seem to be crucial in the response to H2O2 stress.

  18. Toxaphene affects the levels of mRNA transcripts that encode antioxidant enzymes in Hydra.

    Science.gov (United States)

    Woo, Seonock; Lee, Aekyung; Won, Hyokyoung; Ryu, Jae-Chun; Yum, Seungshic

    2012-06-01

    We evaluated toxaphene-induced acute toxicity in Hydra magnipapillata. The median lethal concentrations of the animals (LC(50)) were determined to be 34.5 mg/L, 25.0 mg/L and 12.0 mg/L after exposure to toxaphene for 24 h, 48 h and 72 h, respectively. Morphological responses of hydra polyps to a range of toxaphene concentrations suggested that toxaphene negatively affects the nervous system of H. magnipapillata. We used real-time quantitative PCR of RNA extracted from polyps exposed to two concentrations of toxaphene (0.3 mg/L and 3 mg/L) for 24 h to evaluate the differential regulation of levels of transcripts that encode six antioxidant enzymes (CAT, G6PD, GPx, GR, GST and SOD), two proteins involved in detoxification and molecular stress responses (CYP1A and UB), and two proteins involved in neurotransmission and nerve cell differentiation (AChE and Hym-355). Of the genes involved in antioxidant responses, the most striking changes were observed for transcripts that encode GPx, G6PD, SOD, CAT and GST, with no evident change in levels of transcripts encoding GR. Levels of UB and CYP1A transcripts increased in a dose-dependent manner following exposure to toxaphene. Given that toxaphene-induced neurotoxicity was not reflected in the level of AChE transcripts and only slight accumulation of Hym-355 transcript was observed only at the higher of the two doses of toxaphene tested, there remains a need to identify transcriptional biomarkers for toxaphene-mediated neurotoxicity in H. magnipapillata. Transcripts that respond to toxaphene exposure could be valuable biomarkers for stress levels in H. magnipapillata and may be useful for monitoring the pollution of aquatic environments.

  19. Development and validation of PCR-based assays for diagnosis of American cutaneous leishmaniasis and identification of the parasite species.

    Science.gov (United States)

    Graça, Grazielle Cardoso da; Volpini, Angela Cristina; Romero, Gustavo Adolfo Sierra; Oliveira Neto, Manoel Paes de; Hueb, Marcia; Porrozzi, Renato; Boité, Mariana Côrtes; Cupolillo, Elisa

    2012-08-01

    In this study, PCR assays targeting different Leishmania heat-shock protein 70 gene (hsp70) regions, producing fragments ranging in size from 230-390 bp were developed and evaluated to determine their potential as a tool for the specific molecular diagnosis of cutaneous leishmaniasis (CL). A total of 70 Leishmania strains were analysed, including seven reference strains (RS) and 63 previously typed strains. Analysis of the RS indicated a specific region of 234 bp in the hsp70 gene as a valid target that was highly sensitive for detection of Leishmania species DNA with capacity of distinguishing all analyzed species, after polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). This PCR assay was compared with other PCR targets used for the molecular diagnosis of leishmaniasis: hsp70 (1400-bp region), internal transcribed spacer (ITS)1 and glucose-6-phosphate dehydrogenase (G6pd). A good agreement among the methods was observed concerning the Leishmania species identification. Moreover, to evaluate the potential for molecular diagnosis, we compared the PCR targets hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis protocol.

  20. Clinical analysis of hemolytic anemia in children in Qinghai province%小儿溶血性贫血49例临床分析

    Institute of Scientific and Technical Information of China (English)

    沈红

    2011-01-01

    Objective To analyze the etiology and treatment of hemolytic anemia in children in Qinghai Province. Methods Forty nine patients with hemolytic anemia treated in our hospital from January of 2006 to January of 2010 were retrospectively analyzed. Results G-6-PD deficiency was the most common type of hemolytic anemia, accounting for 59% (29 cases), while autoimmune hemolytic anemia (AIHA) accounted for 22% ( 11 cases), consistent with the characteristics that childhood hemolytic anemia was related with the abnormal internal factors of red blood cells. The clinical manifestations included pale, fever, jaundice, dark urine and hepatosplenomegaly. Conclusions G-6-PD deficiency was the major cause of hemolytic anemia in Qinghai Province. Patients could get good therapeutic effect after effective treatment. Adrenocortical hormone was the first-line drug in AIHA. Blood transfusion needed to be better controlled and monitored.%目的 分析49例溶血性贫血患儿的病因及治疗.方法 对2006年1月-2010年1月期间在我院住院的49例溶血性贫血患儿的临床特点进行回顾性分析.结果 本地区溶血性贫血以G-6-PD缺乏症最多(59%),自身免疫性溶血性贫血次之(22%),符合小儿溶血性贫血多与红细胞内在因素异常有关这一特点.结论 本组病例中G-6-PD缺乏是引起溶血性贫血的主要病因,疗效好.对自身免疫性溶血性贫血肾上腺糖皮质激素是首选药物,输血时应严格配血.

  1. Study on the anesthetic effect of combined intravenous-inhalation general anesthesia under nasopharyngeal airway-mask spontaneous breathing for laparoscopic inguinal hernia surgery in children

    Institute of Scientific and Technical Information of China (English)

    Jing Liu

    2016-01-01

    Objective:To analyze the anesthetic effect of combined intravenous-inhalation general anesthesia under nasopharyngeal airway-mask spontaneous breathing for laparoscopic inguinal hernia surgery in children.Methods:A total of118 cases of children with inguinal hernia who received laparoscopic surgery in our hospital from August 2012 to August 2014 were enrolled as research subjects and randomly divided into observation group 59 cases and control group 59 cases. Control group received conventional tracheal intubation intravenous general anesthesia, observation group received combined intravenous-inhalation general anesthesia under nasopharyngeal airway-mask spontaneous breathing, and then differences in respiratory and circulatory indicators, awareness-related indicators, G-6PD, PFK and inflammatory factor levels and oxidative stress levels between two groups were compared.Results:HR and MAP values of observation group at T1 and T2 were lower than those of control group, and SpO2 value was higher than that of control group; intraoperative Ppeak, Pplat, Raw, D(A-a)O2 and RI levels of observation group were lower than those of control group, and levels of Cdyn and OI were higher than those of control group; intraoperative G-6PD, PFK, CRP and IL-6 levels of observation group were lower than those of control group, and IL-10 level was higher than that of control group; intraoperative NO, SOD and GSH levels of observation group were higher than those of control group, and levels of ET-1, CAT and blood glucose were lower than those of control group.Conclusion:Combined intravenous-inhalation general anesthesia under nasopharyngeal airway-mask spontaneous breathing for laparoscopic inguinal hernia surgery in children can effectively stabilize respiratory and circulatory level, reduce intraoperative systemic inflammation and oxidative stress state and contribute to early postoperative rehabilitation.

  2. Glucose-6-phosphate dehydrogenase deficiency in Tunisia: molecular data and phenotype-genotype association.

    Science.gov (United States)

    Laouini, N; Bibi, A; Ammar, H; Kazdaghli, K; Ouali, F; Othmani, R; Amdouni, S; Haloui, S; Sahli, C A; Jouini, L; Hadj Fredj, S; Siala, H; Ben Romdhane, N; Toumi, N E; Fattoum, S; Messsaoud, T

    2013-02-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. In this study, we aimed to perform a molecular investigation of G6PD deficiency in Tunisia and to associate clinical manifestations and the degree of deficiency with the genotype. A total of 161 Tunisian subjects of both sexes were screened by spectrophotometric assay for enzyme activity. Out of these, 54 unrelated subjects were selected for screening of the most frequent mutations in Tunisia by PCR/RFLP, followed by size-based separation of double-stranded fragments under non-denaturing conditions on a denaturing high performance liquid chromatography system. Of the 56 altered chromosomes examined, 75 % had the GdA(-) mutation, 14.28 % showed the GdB(-) mutation and no mutations were identified in 10.72 % of cases. Hemizygous males with GdA(-) mutation were mostly of class III, while those with GdB(-) mutation were mainly of class II. The principal clinical manifestation encountered was favism. Acute hemolytic crises induced by drugs or infections and neonatal jaundice were also noted. Less severe clinical features such as low back pain were present in heterozygous females and in one homozygous female. Asymptomatic individuals were in majority heterozygote females and strangely one hemizygous male. The spectrum of mutations seems to be homogeneous and similar to that of Mediterranean countries; nevertheless 10.72 % of cases remain with undetermined mutation thus suggesting a potential heterogeneity of the deficiency at the molecular level. On the other hand, we note a better association of the molecular defects with the severity of the deficiency than with clinical manifestations.

  3. Development and validation of PCR-based assays for diagnosis of American cutaneous leishmaniasis and identificatio nof the parasite species

    Directory of Open Access Journals (Sweden)

    Grazielle Cardoso da Graça

    2012-08-01

    Full Text Available In this study, PCR assays targeting different Leishmania heat-shock protein 70 gene (hsp70 regions, producing fragments ranging in size from 230-390 bp were developed and evaluated to determine their potential as a tool for the specific molecular diagnosis of cutaneous leishmaniasis (CL. A total of 70 Leishmania strains were analysed, including seven reference strains (RS and 63 previously typed strains. Analysis of the RS indicated a specific region of 234 bp in the hsp70 gene as a valid target that was highly sensitive for detection of Leishmania species DNA with capacity of distinguishing all analyzed species, after polymerase chain reaction-restriction fragment length polymorfism (PCR-RFLP. This PCR assay was compared with other PCR targets used for the molecular diagnosis of leishmaniasis: hsp70 (1400-bp region, internal transcribed spacer (ITS1 and glucose-6-phosphate dehydrogenase (G6pd. A good agreement among the methods was observed concerning the Leishmania species identification. Moreover, to evaluate the potential for molecular diagnosis, we compared the PCR targets hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis protocol.

  4. Five isozymograms of Trichomonas vaginalis and Trichomonas tenax: A comparative study%阴道毛滴虫和口腔毛滴虫5种同工酶谱对比分析

    Institute of Scientific and Technical Information of China (English)

    梁裕芬; 韦俊彬; 运晨霞; 黄庶识

    2010-01-01

    目的 分析阴道毛滴虫(Trichomonas vaginalis,Tv)和口腔毛滴虫(Trichomonas tenax,TT)的同工谱特征及其亲缘关系,寻找同工酶谱鉴别指标.方法 采用聚丙烯酰胺凝胶垂直板电泳,分别进行苹果酸脱氢酶(malate dehydrogenase, MDH)、谷氨酸脱氢酶(glutamic dehydrogenase, GLDH)、6-磷酸-葡萄糖脱氧酶(glucose-6-phosphate dehydrogenase, G6PD)、乙醇脱氢酶(alcohol dehydrogenase, ADH)和过氧化氢酶(Catalase)5种同工酶染色,比较分析2种滴虫的酶谱.结果 MDH同工酶:2种滴虫只有相对迁移率(Rm) 52、85 2条区带相同,而Rm 34、42、94、100 4条区带在2种滴虫之间明显不同;GLDH同工酶:TV无显带,TT共分离出6条酶带;G6PD同工酶:TV只有Rm35、42、52 3条区带,而TT除了显示这3条区带外,还显示出其他迁移率更大的区带;ADH和Catalase均无区带显示.结论 MDH、GLDH和G6PD3种同工酶均具有鉴别意义.

  5. Suicide for survival--death of infected erythrocytes as a host mechanism to survive malaria.

    Science.gov (United States)

    Föller, Michael; Bobbala, Diwakar; Koka, Saisudha; Huber, Stephan M; Gulbins, Erich; Lang, Florian

    2009-01-01

    The pathogen of malaria, Plasmodium, enters erythrocytes and thus escapes recognition by the immune system. The pathogen induces oxidative stress to the host erythrocyte, which triggers eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are identified by macrophages which engulf and degrade the eryptotic cells. To the extent that infected erythrocytes undergo eryptosis prior to exit of Plasmodiaand subsequent infection of other erythrocytes, the premature eryptosis may protect against malaria. Accordingly, any therapeutical intervention accelerating suicidal death of infected erythrocytes has the potential to foster elimination of infected erythrocytes, delay the development of parasitemia and favorably influence the course of malaria. Eryptosis is stimulated by a wide variety of triggers including osmotic shock, oxidative stress, energy depletion and a wide variety of xenobiotics. Diseases associated with accelerated eryptosis include sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson's disease. Among the known stimulators of eryptosis, paclitaxel, chlorpromazine, cyclosporine, curcumin, PGE2 and lead have indeed been shown to favourably influence the course of malaria. Moreover, sickle-cell trait, beta-thalassemia trait, glucose-6-phosphate dehydrogenase (G6PD)-deficiency and iron deficiency confer some protection against a severe course of malaria. Importantly, counteracting Plasmodia by inducing eryptosis is not expected to generate resistance of the pathogen, as the proteins involved in suicidal death of the host cell are not encoded by the pathogen and thus cannot be modified by mutations of its genes.

  6. 镰状细胞综合征的血液学和临床特点研究%Study on the Hematology and Clinical Characteristics of Sickle Cell Syndromes

    Institute of Scientific and Technical Information of China (English)

    葛艳芬; 李萍; 王景健; 黄锦维; 谢红东; 林乘龙

    2015-01-01

    目的:通过总结34例镰状细胞综合征(HbS 病)患者的血液学指标,分析其所导致的血液学和临床特点。方法选取2005年3月—2013年11月于广东省人民医院就诊的 HbS 病患者34例为研究对象,早晨空腹负压抽取静脉血进行血常规分析、血红蛋白(Hb)电泳分析、红细胞镰变试验、变性珠蛋白小体(Heinz 小体)试验、铁蛋白检测及葡萄糖-6-磷酸脱氢酶/6-磷酸葡萄糖酸脱氢酶(G6PD/6PGD)检测。结果 4例血红蛋白 S(HbS)纯合子患儿均未见正常 HbA 区带,大部分以 HbS 区带为主,少量HbA2区带;呈中度贫血。有3个 HbS 纯合子家系,父母均为 HbS 杂合子。HbS 杂合子成人患者中只有5例 Hb 在92~97 g/ L,呈轻度贫血,其余患者 Hb 均>110 g/ L。HbS 杂合子新生儿患者中 HbS 含量低,低于7.00%。胎儿脐血和新生儿各有1例同时出现 HbS 和 Hb Barts 区带,提示HbS -α地中海贫血。1例孕妇是 HbS 杂合子,孕32周+6行胎儿脐血分析是HbS -α地中海贫血。1例男婴的血常规分析与 Hb电泳分析结果提示其为HbS -β地中海贫血。婴儿、儿童、成人红细胞镰变试验阳性。4例成人HbS -α地中海贫血患者Heinz 小体试验为阳性。1例 HbS 杂合子患者铁蛋白低,为2.4μg/ L。4例男性 HbS 杂合子患者 G6PD/6PGD 为0.11~0.29,3例女性 HbS 杂合子患者 G6PD/6PGD 为0.51~ 0.70。结论 HbS 纯合子患者因 HbS 取代了正常的 HbA,容易导致血管栓塞,引起慢性溶血性贫血等临床症状,呈中度贫血;HbS 杂合子大部分不会对个体的临床表型产生影响,所以一般无临床症状或极少数症状较轻;HbS -α地中海贫血、HbS -β地中海贫血均可引起轻度贫血;HbS 杂合子合并缺铁性贫血、HbS 杂合子合并 G6PD 缺乏可加重贫血症状,呈中度贫血。%Objective To summarize hematological indicators of 34 cases of sickle cell syndrome( Hb

  7. The association between malaria parasitaemia, erythrocyte polymorphisms, malnutrition and anaemia in children less than 10 years in Senegal: a case control study

    Directory of Open Access Journals (Sweden)

    Tine Roger CK

    2012-10-01

    Full Text Available Abstract Background Malaria and anaemia (Haemoglobin Methods Study participants were randomly selected from a list of children who participated in a survey in December 2010. Children aged from 1 to 10 years with haemoglobin level below 11 g/dl represented cases (anaemic children. Control participants were eligible if of same age group and their haemoglobin level was >= 11 g/dl. For each participant, a physical examination was done and anthropometric data collected prior to a biological assessment which included: malaria parasitaemia infection, intestinal worm carriage, G6PD deficiency, sickle cell disorders, and alpha-talassaemia. Results Three hundred and fifty two children 5 years (aOR=0.03, 95%CI[0.01-0.08]. Stratified by age group, anaemia was significantly associated with stunting in children less than 5 years (aOR=3.1 95%CI[1.4 – 6.8], with, sickle cell disorders (aOR=3.5 95%CI [1.4 – 9.0], alpha-thalassemia (or=2.4 95%CI[1.1–5.3] and stunting (aOR=3.6 95%CI [1.6–8.2] for children above 5 years. No association was found between G6PD deficiency, intestinal worm carriage and children’s gender. Conclusion Malaria parasitaemia, stunting and haemoglobin genetic disorders represented the major causes of anaemia among study participants. Anaemia control in this area could be achieved by developing integrated interventions targeting both malaria and malnutrition.

  8. Roles of glucose-6-phosphate dehydrogenase in obesity induced by high fat diet%葡萄糖-6-磷酸脱氢酶在高脂饲料诱导肥胖中的作用

    Institute of Scientific and Technical Information of China (English)

    吴春艳; 王芳; 芦建慧; 赵艳

    2013-01-01

    Objective To explore the roles of glucose-6-phosphate dehydrogenase (G6PD) and its downstream NADPH oxidase (NOX) in obesity induced by high fat diet.Methods 40 male Wistar rats were randomly divided into a high fat diet group (30 rats)and a control group (10 rats) fed with rat chow.After six weeks,rats fed with high fat diet were screened out obesity-prone group and obesity-resistant group based on the gain of body weight.obesity-prone group and obesity-resistant group rats continued to be fed with high fat diet.Basic diet group served as normal control.All rats were killed after 13 weeks.Biochemical markers and G6PD activity were determined in adipose tissues.The expression of G6PD and the NOX subunit of P22 gene were detected using RT-PCR.Results Blood glucose levels were higher in obesity-prone group rats than those in control rats (P < 0.05).Triglyceride levels and body fat contents were significantly higher in OP rats than that in obesity-resistant group rats(P < 0.05).Insulin,insulin resistant index,body weight were significantly higher in obesity-prone group rats than that in control and obesity-resistant group rats (P < 0.05).There was no significant difference between the control and obesity-resistant group rats.The activity and expression of G6PD in the obesity-prone group rats were lower than those in the control and obesity-resistant group rats(P < 0.05).The expression of P22 subunit in the obesity-prone group rats was significantly higher than that in the control and obesity-resistant group rats (P < 0.05),but there was no significant difference between the control and OR rats.Conclusion G6PD and its downsream NAPDH oxidase may play an important role in the pathogenesis and development of obesity.%目的 探讨葡萄糖-6-磷酸脱氢酶(G6PD)及其下游NADPH氧化酶在高脂饲料诱导肥胖中的作用.方法 40只雄性Wistar大鼠随机分为高脂饲料组(30只)和基础饲料组(10只),6周后,高脂饲料组依据体

  9. Characterization of the Minimum Energy Paths for the Ring Closure Reactions of C4H3 with Acetylene

    Science.gov (United States)

    Walch, Stephen P.

    1995-01-01

    The ring closure reaction of C4H3 with acetylene to give phenyl radical is one proposed mechanism for the formation of the first aromatic ring in hydrocarbon combustion. There are two low-lying isomers of C4H3; 1-dehydro-buta-l-ene-3-yne (n-C4H3) and 2-dehydro-buta-l-ene-3-yne (iso-C4H3). It has been proposed that only n-C4H3 reacts with acetylene to give phenyl radical, and since iso-C4H3 is more stable than n-C4H3, formation of phenyl radical by this mechanism is unlikely. We report restricted Hartree-Fock (RHF) plus singles and doubles configuration interaction calculations with a Davidson's correction (RHF+1+2+Q) using the Dunning correlation consistent polarized valence double zeta basis set (cc-pVDZ) for stationary point structures along the reaction pathway for the reactions of n-C4H3 and iso-C4H3 with acetylene. n-C4H3 plus acetylene (9.4) has a small entrance channel barrier (17.7) (all energetics in parentheses are in kcal/mol with respect to iso-C4H3 plus acetylene) and the subsequent closure steps leading to phenyl radical (-91.9) are downhill with respect to the entrance channel barrier. Iso-C4H3 Plus acetylene also has an entrance channel barrier (14.9) and there is a downhill pathway to 1-dehydro-fulvene (-55.0). 1-dehydro-fulvene can rearrange to 6-dehydro-fulvene (-60.3) by a 1,3-hydrogen shift over a barrier (4.0), which is still below the entrance channel barrier, from which rearrangement to phenyl radical can occur by a downhill pathway. Thus, both n-C4H3 and iso-C4H3 can react with acetylene to give phenyl radical with small barriers.

  10. Use of liquid chromatography coupled to low- and high-resolution linear ion trap mass spectrometry for studying the metabolism of paynantheine, an alkaloid of the herbal drug Kratom in rat and human urine.

    Science.gov (United States)

    Philipp, Anika A; Wissenbach, Dirk K; Weber, Armin A; Zapp, Josef; Zoerntlein, Siegfried W; Kanogsunthornrat, Jidapha; Maurer, Hans H

    2010-04-01

    The Thai medicinal plant Mitragyna speciosa (Kratom in Thai) is misused as a herbal drug of abuse. During studies on the main Kratom alkaloid mitragynine (MG) in rats and humans, several dehydro analogs could be detected in urine of Kratom users, which were not found in rat urine after administration of pure MG. Questions arose as to whether these compounds are formed from MG only by humans or whether they are metabolites formed from the second abundant Kratom alkaloid paynantheine (PAY), the dehydro analog of MG. Therefore, the aim of the presented study was to identify the phase I and II metabolites of PAY in rat urine after administration of the pure alkaloid. This was first isolated from Kratom leaves. Liquid chromatography-linear ion trap mass spectrometry provided detailed structure information of the metabolites in the MS(n) mode particularly with high resolution. Besides PAY, the following phase I metabolites could be identified: 9-O-demethyl PAY, 16-carboxy PAY, 9-O-demethyl-16-carboxy PAY, 17-O-demethyl PAY, 17-O-demethyl-16,17-dihydro PAY, 9,17-O-bisdemethyl PAY, 9,17-O-bisdemethyl-16,17-dihydro PAY, 17-carboxy-16,17-dihydro PAY, and 9-O-demethyl-17-carboxy-16,17-dihydro PAY. These metabolites indicated that PAY was metabolized via the same pathways as MG. Several metabolites were excreted as glucuronides or sulfates. The metabolism studies in rats showed that PAY and its metabolites corresponded to the MG-related dehydro compounds detected in urine of the Kratom users. In conclusion, PAY and its metabolites may be further markers for a Kratom abuse in addition of MG and its metabolites.

  11. Summer (subarctic) versus winter (subtropic) production affects spinach (Spinacia oleracea L.) leaf bionutrients: vitamins (C, E, Folate, K1, provitamin A), lutein, phenolics, and antioxidants.

    Science.gov (United States)

    Lester, Gene E; Makus, Donald J; Hodges, D Mark; Jifon, John L

    2013-07-24

    Comparison of spinach (Spinacia oleracea L.) cultivars Lazio and Samish grown during the summer solstice in the subarctic versus the winter solstice in the subtropics provided insight into interactions between production environment (light intensity), cultivar, and leaf age/maturity/position affecting bionutrient concentrations of vitamins (C, E, folate, K1, provitamin A), lutein, phenolics, and antioxidants. Growing spinach during the winter solstice in the subtropics resulted in increased leaf dry matter %, oxidized (dehydro) ascorbic acid (AsA), α- and γ-tocopherol, and total phenols but lower reduced (free) AsA, α-carotene, folate, and antioxidant capacity compared to summer solstice-grown spinach in the subarctic. Both cultivars had similar bionutrients, except for higher dehydroAsA, and lower α- and γ-tocopherol in 'Samish' compared to 'Lazio'. For most bionutrients measured, there was a linear, and sometimes quadratic, increase in concentrations from bottom to top canopy leaves. However, total phenolics and antioxidant capacity increased basipetally. The current study has thus demonstrated that dehydroAsA, α-tocopherol, and γ-tocopherol were substantially lower in subarctic compared to subtropical-grown spinach, whereas the opposite relationship was found for antioxidant capacity, α-carotene, and folates (vitamin B9). The observations are consistent with previously reported isolated effects of growth environment on bionutrient status of crops. The current results clearly highlight the effect of production environment (predominantly radiation capture), interacting with genetics and plant phenology to alter the bionutrient status of crops. While reflecting the effects of changing growing conditions, these results also indicate potential alterations in the nutritive value of foods with anticipated shifts in global climatic conditions.

  12. Clinical rounds in the well-baby nursery: treating jaundiced newborns.

    Science.gov (United States)

    Maisels, M J

    1995-10-01

    Ten pearls (and pitfalls) in the management of the jaundiced newborn: Remember to take a history. Ask about jaundice in previous siblings and check family ethnicity. Don't ignore jaundice in the first 24 hours--it is considered pathologic until proven otherwise. Some normal infants may appear jaundiced and have a bilirubin level of 5 mg/dL at 23 hours and 59 minutes. On the other hand, a bilirubin level of 5 mg/dL at 10 hours is almost certainly pathologic. Use your judgment. Don't treat 35 to 37 week gestation infants as if they were full-term infants. Although these babies are cared for in well-baby nurseries and are generally treated like full-term infants, they are not full term. They are not as vigorous and do not nurse as well as full-term infants. Infants at 37 weeks gestation are four times more likely to have a serum bilirubin level greater than 13 mg/dL than those at 40 weeks gestation. Don't send 35-week gestation infants home before 48 hours. Document your assessment, particularly if the infant is being discharged early. Document the presence or absence of jaundice and its severity. A late rising bilirubin is typical of G6PD deficiency. Think about the ethnic background: G6PD deficiency is much more likely to occur in families from Greece, Turkey, Sardinia, and Nigeria, and particularly in Sephardic Jews from Iraq, Iran, Syria, and Kurdistan. Your practice may not contain many such families but remember in today's world of travel and intermarriage, etc, these genes are ubiquitous and the diagnosis of G6PD deficiency should always be considered in a newborn child with a significant elevation of bilirubin, particularly if it is a male and the rise in bilirubin is of late onset. Don't use homeopathic doses of phototherapy. As with any drug, phototherapy should be provided in a therapeutic dose (see above), but with the light sources commonly used, it is impossible to overdose the patient. Don't ignore a failure of response to phototherapy. If the bilirubin

  13. Enzymatic synthesis of bioactive compounds by Rhus laccase from Chinese Rhus vernicifera

    Institute of Scientific and Technical Information of China (English)

    AKIYAMA; Kazuhiro; MIYAKOSHI; Tetsuo

    2007-01-01

    A simple one step synthesis of pinoresinol and its derivatives-active components of Du-Zhong(Eu-commia ulmoides) -from coniferyl alcohol and p-courmaryl alcohol with higher yields was achieved by Rhus laccases(RL) catalysis in water miscible organic solvents. Biomacromolecules dehydro-genative polymers(DHP) were only synthesized by fungal laccases,not by RL. The structures and the reaction mechanism were discussed to promote the understanding of the function of laccases in the process of lignin biosynthesis.

  14. Occurrence of L-Ascorbic Acid in Euglena gracilis z

    OpenAIRE

    1980-01-01

    Euglena gracilis synthesizes L-ascorbic acid. The content of total L-ascorbic acid in the cells grown photoautotrophically for 9 days in the stationary phase was 4.01 μmole/10^9 cells, corresponding to 4.25 mg per g dry weight. The oxidized form, dehydro-L-ascorbic acid was about 20% of total L-ascorbic acid. Illumination influenced the acid content markedly. From the present data, formation and physiological roles of L-ascorbic acid seem to be strongly affected by illumination.

  15. Diterpenoid acids from Grindelia nana.

    Science.gov (United States)

    Mahmoud, A A; Ahmed, A A; Tanaka, T; Iinuma, M

    2000-03-01

    Two new norditerpenoid acids of the labdane-type (norgrindelic acids), 4,5-dehydro-6-oxo-18-norgrindelic acid (1) and 4beta-hydroxy-6-oxo-19-norgrindelic acid (2), as well as a new grindelic acid derivative, 18-hydroxy-6-oxogrindelic acid (3), were isolated from the aerial parts of Grindelia nana. In addition, the known compounds, 6-oxogrindelic acid, grindelic acid, methyl grindeloate, 7alpha,8alpha-epoxygrindelic acid, and 4alpha-carboxygrindelic acid were also isolated. The structures of the new compounds were characterized on the basis of spectroscopic analysis.

  16. [Corticosteroid hormones in the blood and adrenals of the aurochs Bison bonasus].

    Science.gov (United States)

    Belova, T A; Kuntsevich, M V

    1978-01-01

    Using thin-layer chromatography, studies have been made on corticosteroids in the aurochs Bison bonasus. Hydrocortison, corticosteron, aldosteron, 11-dehydrocorticosteron and 11-deoxycorticosteron were found in the suprarenals. Besides these hormones, the blood of the aurochs contains cortison, 17-oxy-11-deoxycorticosteron ("S" compounds) and unidentified fraction. Compounds revealed in the blood of the aurochs were also found in the bison and ox. The ratio of hydrocortison to corticosteron together with 11-dehydro- and 11-deoxycorticosteron is equal to 0.42 +/- 0.06 in the suprarenals and to 0.34 +/- 0.01 in the blood.

  17. Synthesis, photophysics, electrochemistry, thermal stability and electroluminescent performances of a new europium complex with bis(β-diketone) ligand containing carbazole group.

    Science.gov (United States)

    Liu, Jian; Liang, Quan-Bin; Wu, Hong-Bin

    2016-09-07

    We synthesized a new europium complex [Eu(ecbpd)3 (Phen)] with bis(β-diketone) ligand containing a carbazole group, in which ecbpd and Phen are dehydro-3,3'-(9-ethyl-9H-carbazole-3,6-diyl)bis(1-phenylpropane-1,3-dione) and 1,10-phenanthroline, respectively. Its UV/vis and photoluminescent spectra, quantum yield, luminescence lifetime, electrochemistry, thermal stability and electroluminescent performances were studied. This europium complex showed low efficiency luminescence, which is probably due to the mismatching energy levels of its ligand and Eu(3)(+) , as well as the double Eu(3)(+) core resonance.

  18. The plant cuticle is required for osmotic stress regulation of abscisic acid biosynthesis and osmotic stress tolerance in Arabidopsis

    KAUST Repository

    Wang, Zhenyu

    2011-05-01

    Osmotic stress activates the biosynthesis of abscisic acid (ABA). One major step in ABA biosynthesis is the carotenoid cleavage catalyzed by a 9-cis epoxycarotenoid dioxygenase (NCED). To understand the mechanism for osmotic stress activation of ABA biosynthesis, we screened for Arabidopsis thaliana mutants that failed to induce the NCED3 genee xpression in response to osmotic stress treatments. The ced1 (for 9-cis epoxycarotenoid dioxy genase defective 1) mutant isolated in this study showed markedly reduced expression of NCED3 in response to osmotic stress (polyethylene glycol)treatments compared with the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress. ced1 mutant plants are very sensitive to even mild osmotic stress. Map-based cloning revealed unexpectedly thatCED1 encodes a putative a/b hydrolase domain-containing protein and is allelic to the BODYGUARD gene that was recently shown to be essential for cuticle biogenesis. Further studies discovered that other cut in biosynthesis mutants are also impaired in osmotic stress induction of ABA biosynthesis genes and are sensitive to osmotic stress. Our work demonstrates that the cuticle functions not merely as a physical barrier to minimize water loss but also mediates osmotic stress signaling and tolerance by regulating ABA biosynthesis and signaling. © 2011 American Society of Plant Biologists. All rights reserved.

  19. Modulation of key metabolic enzyme of Labeo rohita (Hamilton) juvenile: effect of dietary starch type, protein level and exogenous alpha-amylase in the diet.

    Science.gov (United States)

    Kumar, Shivendra; Sahu, N P; Pal, A K; Sagar, Vidya; Sinha, Amit Kumar; Baruah, Kartik

    2009-06-01

    A 60-day feeding trial was conducted to delineate the effect of both gelatinized (G) and non-gelatinized (NG) corn with or without supplementation of exogenous alpha-amylase, either at optimum (35%) or sub-optimum (27%) protein levels, on blood glucose, and the key metabolic enzymes of glycolysis (hexokinase, HK), gluconeogenesis (glucose-6 phosphatase, G6Pase and fructose-1,6 bisphosphatase, FBPase), lipogenesis (glucose-6 phosphate dehydrogenase, G6PD) and amino acid metabolism (alanine amino transferase, ALT and aspartate amino transferase, AST) in Labeo rohita. Three hundred and sixty juveniles (average weight 10 +/- 0.15 g) were randomly distributed into 12 treatment groups with each of two replicates. Twelve semi-purified diets containing either 35 or 27% crude protein were prepared by including G or NG corn as carbohydrate source with different levels of microbial alpha-amylase (0, 50, 100 and 150 mg kg(-1)). The G corn fed groups showed significantly higher (P amylase level in diet or their interaction had no significant effect (P > 0.05) on liver HK activity, but the optimum crude protein (35%) fed group showed higher HK activity than their low protein counterparts. The sub-optimum crude protein (27%) fed group showed significantly higher (P amylase kg(-1) feed showed increased blood glucose and G6PD activity of the NG corn fed group, whereas the reverse trend was found for G6Pase, FBPase, ALT and AST activity in liver, which was similar to that of the G or NG corn supplemented with 100/150 mg alpha-amylase kg(-1) feed. Data on enzyme activities suggest that NG corn in the diet significantly induced more gluconeogenic and amino acid metabolic enzyme activity, whereas G corn induced increased lipogenic enzyme activity. Increased amino acid catabolic enzyme (ALT and AST) activity was observed either at optimum protein (35%) irrespective of corn type or NG corn without supplementation of alpha-amylase irrespective of protein level in the diet.

  20. Enzymes and membrane proteins of ADSOL-preserved red blood cells

    Directory of Open Access Journals (Sweden)

    Maria Sueli Soares Leonart

    2000-03-01

    Full Text Available CONTEXT: The preservative solution ADSOL (adenine, dextrose, sorbitol, sodium chloride and mannitol maintains red cell viability for blood trans-fusion for 6 weeks. It would be useful to know about its preservation qualities over longer periods. OB